Abstract
Purpose
Stem cells are characterized by the capability of self-renewal and multi-differentiation. Normal stem cells, which are important for tissue repair and tissue regeneration, can be divided into embryonic stem cells (ESCs) and somatic stem cells (SSCs) depending on their origin. As a subpopulation of cells within cancer, cancer stem cells (CSCs) are at the root of therapeutic resistance. Tumor-initiating cells (TICs) are necessary for tumor initiation. Caveolin1 (Cav1), a membrane protein located at the caveolae, participates in cell lipid transport, cell migration, cell proliferation, and cell signal transduction. The purpose of this review was to explore the relationship between Cav1 and stem cells.
Results
In ESCs, Cav1 is beneficial for self-renewal, proliferation, and migration. In SSCs, Cav1 exhibits positive or/and negative effects on stem cell self-renewal, differentiation, proliferation, migration, and angiogenic capacity. Cav1 deficiency impairs normal stem cell-based tissue repair. In CSCs, Cav1 inhibits or/and promotes CSC self-renewal, differentiation, invasion, migration, tumorigenicity ability, and CSC formation. And suppressing Cav1 promotes chemo-sensitivity in CSCs and TICs.
Conclusion
Cav1 shows dual roles in stem cell biology. Targeting the Cav1-stem cell axis would be a new way for tissue repair and cancer drug resistance.
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Code availability
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References
Ahmed SA, Parama D, Daimari E, Girisa S, Banik K, Harsha C, Dutta U, Kunnumakkara AB (2020) Rationalizing the therapeutic potential of apigenin against cancer. Life Sci. https://doi.org/10.1016/j.lfs.2020.118814
Akunuru S, Geiger H (2016) Aging, clonality, and rejuvenation of hematopoietic stem cells. Trends Mol Med 22(8):701–712. https://doi.org/10.1016/j.molmed.2016.06.003
Ambasta RK, Kohli H, Kumar P (2017) Multiple therapeutic effect of endothelial progenitor cell regulated by drugs in diabetes and diabetes related disorder. J Transl Med 15(1):185. https://doi.org/10.1186/s12967-017-1280-y
Bai L, Shi G, Zhang L, Guan F, Ma Y, Li Q, Cong YS, Zhang L (2014) Cav-1 deletion impaired hematopoietic stem cell function. Cell Death Dis 5(3):e1140. https://doi.org/10.1038/cddis.2014.105
Bai X, Ni J, Beretov J, Graham P, Li Y (2018) Cancer stem cell in breast cancer therapeutic resistance. Cancer Treat Rev 69:152–163. https://doi.org/10.1016/j.ctrv.2018.07.004
Bai L, Lyu Y, Shi G, Li K, Huang Y, Ma Y, Cong YS, Zhang L, Qin C (2020) Polymerase I and transcript release factor transgenic mice show impaired function of hematopoietic stem cells. Aging 12(20):20152–20162. https://doi.org/10.18632/aging.103729
Baker N, Tuan RS (2013) The less-often-traveled surface of stem cells: caveolin-1 and caveolae in stem cells, tissue repair and regeneration. Stem Cell Res Ther 4(4):90. https://doi.org/10.1186/scrt276
Baker N, Zhang G, You Y, Tuan RS (2012) Caveolin-1 regulates proliferation and osteogenic differentiation of human mesenchymal stem cells. J Cell Biochem 113(12):3773–3787. https://doi.org/10.1002/jcb.24252
Baker N, Sohn J, Tuan RS (2015) Promotion of human mesenchymal stem cell osteogenesis by PI3-kinase/Akt signaling, and the influence of caveolin-1/cholesterol homeostasis. Stem Cell Res Ther 6:238. https://doi.org/10.1186/s13287-015-0225-8
Bandara N, Gurusinghe S, Lim SY, Chen H, Chen S, Wang D, Hilbert B, Wang LX, Strappe P (2016) Molecular control of nitric oxide synthesis through eNOS and caveolin-1 interaction regulates osteogenic differentiation of adipose-derived stem cells by modulation of Wnt/β-catenin signaling. Stem Cell Res Ther 7(1):182. https://doi.org/10.1186/s13287-016-0442-9
Bandara N, Gurusinghe S, Kong A, Mitchell G, Wang LX, Lim SY, Strappe P (2019) Generation of a nitric oxide signaling pathway in mesenchymal stem cells promotes endothelial lineage commitment. J Cell Physiol 234(11):20392–20407. https://doi.org/10.1002/jcp.28640
Bankaitis ED, Ha A, Kuo CJ, Magness ST (2018) Reserve stem cells in intestinal homeostasis and injury. Gastroenterology 155(5):1348–1361. https://doi.org/10.1053/j.gastro.2018.08.016
Beattie R, Hippenmeyer S (2017) Mechanisms of radial glia progenitor cell lineage progression. FEBS Lett 591(24):3993–4008. https://doi.org/10.1002/1873-3468.12906
Belaadi N, Aureille J, Guilluy C (2016) Under pressure: mechanical stress management in the nucleus. Cells. https://doi.org/10.3390/cells5020027
Bernatchez P, Sharma A, Bauer PM, Marin E, Sessa WC (2011) A noninhibitory mutant of the caveolin-1 scaffolding domain enhances eNOS-derived NO synthesis and vasodilation in mice. J Clin Investig 121(9):3747–3755. https://doi.org/10.1172/jci44778
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
Cabarcas SM, Sun L, Mathews L, Thomas S, Zhang X, Farrar WL (2013) The differentiation of pancreatic tumor-initiating cells by vitronectin can be blocked by cilengitide. Pancreas 42(5):861–870. https://doi.org/10.1097/MPA.0b013e318279d568
Campos A, Burgos-Ravanal R, González MF, Huilcaman R, Lobos González L, Quest AFG (2019) Cell intrinsic and extrinsic mechanisms of caveolin-1-enhanced metastasis. Biomolecules. https://doi.org/10.3390/biom9080314
Cao H, Courchesne WE, Mastick CC (2002) A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase. J Biol Chem 277(11):8771–8774. https://doi.org/10.1074/jbc.C100661200
Cao C, Zhang H, Gong L, He Y, Zhang N (2012) High glucose conditions suppress the function of bone marrow-derived endothelial progenitor cells via inhibition of the eNOS-caveolin-1 complex. Mol Med Rep 5(2):341–346. https://doi.org/10.3892/mmr.2011.644
Case N, Xie Z, Sen B, Styner M, Zou M, O’Conor C, Horowitz M, Rubin J (2010) Mechanical activation of β-catenin regulates phenotype in adult murine marrow-derived mesenchymal stem cells. J Orthop Res 28(11):1531–1538. https://doi.org/10.1002/jor.21156
Chatterjee M, Ben-Josef E, Robb R, Vedaie M, Seum S, Thirumoorthy K, Palanichamy K, Harbrecht M, Chakravarti A, Williams TM (2017) Caveolae-mediated endocytosis is critical for albumin cellular uptake and response to albumin-bound chemotherapy. Cancer Res 77(21):5925–5937. https://doi.org/10.1158/0008-5472.can-17-0604
Chatterji P, Douchin J, Giroux V (2018) Demystifying the differences between tumor-initiating cells and cancer stem cells in colon cancer. Curr Colorectal Cancer Rep 14(4):242–250
Chen D, Che G (2014) Value of caveolin-1 in cancer progression and prognosis: emphasis on cancer-associated fibroblasts, human cancer cells and mechanism of caveolin-1 expression (review). Oncol Lett 8(4):1409–1421. https://doi.org/10.3892/ol.2014.2385
Chen Y, Wang C, Huang Q, Wu D, Cao J, Xu X, Yang C, Li X (2017) Caveolin-1 plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells into cardiomyocytes. Cardiology 136(1):40–48. https://doi.org/10.1159/000446869
Cheng JPX, Nichols BJ (2016) Caveolae: one function or many? Trends Cell Biol 26(3):177–189. https://doi.org/10.1016/j.tcb.2015.10.010
Chidlow JH Jr, Sessa WC (2010) Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation. Cardiovasc Res 86(2):219–225. https://doi.org/10.1093/cvr/cvq075
Chiodi I, Mondello C (2020) Life style factors, tumor cell plasticity and cancer stem cells. Mutat Res 784:108308. https://doi.org/10.1016/j.mrrev.2020.108308
Clara JA, Monge C, Yang Y, Takebe N (2020) Targeting signalling pathways and the immune microenvironment of cancer stem cells—a clinical update. Nat Rev Clin Oncol 17(4):204–232. https://doi.org/10.1038/s41571-019-0293-2
Dai X, Zhai L, Su Q, Luo B, Wei C, Liu Y, Huang Y, Ma C, Ying Y (2020) Effect of aerobic and resistance training on endothelial progenitor cells in mice with type 2 diabetes. Cell Reprogram 22(4):189–197. https://doi.org/10.1089/cell.2019.0063
de Sousa MC, Gjorgjieva M, Dolicka D, Sobolewski C, Foti M (2019) Deciphering miRNAs’ action through miRNA editing. Int J Mol Sci. https://doi.org/10.3390/ijms20246249
Del Prete A, Schioppa T, Tiberio L, Stabile H, Sozzani S (2017) Leukocyte trafficking in tumor microenvironment. Curr Opin Pharmacol 35:40–47. https://doi.org/10.1016/j.coph.2017.05.004
Díaz J, Mendoza P, Ortiz R, Díaz N, Leyton L, Stupack D, Quest AFG, Torres VA (2014) Rab5 is required in metastatic cancer cells for caveolin-1-enhanced Rac1 activation, migration and invasion. J Cell Sci 127(Pt 11):2401–2406. https://doi.org/10.1242/jcs.141689
Dong J, Ma Q (2019) Integration of inflammation, fibrosis, and cancer induced by carbon nanotubes. Nanotoxicology 13(9):1244–1274. https://doi.org/10.1080/17435390.2019.1651920
Du J, Chen X, Liang X, Zhang G, Xu J, He L, Zhan Q, Feng XQ, Chien S, Yang C (2011) Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity. Proc Natl Acad Sci USA 108(23):9466–9471. https://doi.org/10.1073/pnas.1106467108
Du C, Chen L, Zhang H, Wang Z, Liu W, Xie X, Xie M (2014) Caveolin-1 limits the contribution of BKCa channel to MCF-7 breast cancer cell proliferation and invasion. Int J Mol Sci 15(11):20706–20722. https://doi.org/10.3390/ijms151120706
Fan ST, Yang ZF, Ho DW, Ng MN, Yu WC, Wong J (2011) Prediction of posthepatectomy recurrence of hepatocellular carcinoma by circulating cancer stem cells: a prospective study. Ann Surg 254(4):569–576. https://doi.org/10.1097/SLA.0b013e3182300a1d
Fan XL, Zhang Y, Li X, Fu QL (2020) Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci 77(14):2771–2794. https://doi.org/10.1007/s00018-020-03454-6
Feng Y, Jiang W, Zhao W, Lu Z, Gu Y, Dong Y (2020) miR-124 regulates liver cancer stem cells expansion and sorafenib resistance. Exp Cell Res 394(2):112162. https://doi.org/10.1016/j.yexcr.2020.112162
Filippini A, D’Alessio A (2020) Caveolae and lipid rafts in endothelium: valuable organelles for multiple functions. Biomolecules. https://doi.org/10.3390/biom10091218
Fong JT, Nimlamool W, Falk MM (2014) EGF induces efficient Cx43 gap junction endocytosis in mouse embryonic stem cell colonies via phosphorylation of Ser262, Ser279/282, and Ser368. FEBS Lett 588(5):836–844. https://doi.org/10.1016/j.febslet.2014.01.048
Guan X, Wang N, Cui F, Liu Y, Liu P, Zhao J, Han C, Li X, Leng Z, Li Y, Ji X, Zou W, Liu J (2016) Caveolin-1 is essential in the differentiation of human adipose-derived stem cells into hepatocyte-like cells via an MAPK pathway-dependent mechanism. Mol Med Rep 13(2):1487–1494. https://doi.org/10.3892/mmr.2015.4743
Gupta VK, Sharma NS, Kesh K, Dauer P, Nomura A, Giri B, Dudeja V, Banerjee S, Bhattacharya S, Saluja A, Banerjee S (2018) Metastasis and chemoresistance in CD133 expressing pancreatic cancer cells are dependent on their lipid raft integrity. Cancer Lett 439:101–112. https://doi.org/10.1016/j.canlet.2018.09.028
Hall A, Lalli G (2010) Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb Perspect Biol 2(2):a001818. https://doi.org/10.1101/cshperspect.a001818
Han C, Wang YJ, Wang YC, Guan X, Wang L, Shen LM, Zou W, Liu J (2021) Caveolin-1 downregulation promotes the dopaminergic neuron-like differentiation of human adipose-derived mesenchymal stem cells. Neural Regen Res 16(4):714–720. https://doi.org/10.4103/1673-5374.295342
Hansen CG, Nichols BJ (2010) Exploring the caves: cavins, caveolins and caveolae. Trends Cell Biol 20(4):177–186. https://doi.org/10.1016/j.tcb.2010.01.005
Harvey A, Caretti G, Moresi V, Renzini A, Adamo S (2019) Interplay between metabolites and the epigenome in regulating embryonic and adult stem cell potency and maintenance. Stem Cell Rep 13(4):573–589. https://doi.org/10.1016/j.stemcr.2019.09.003
Hill MM, Bastiani M, Luetterforst R, Kirkham M, Kirkham A, Nixon SJ, Walser P, Abankwa D, Oorschot VM, Martin S, Hancock JF, Parton RG (2008) PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 132(1):113–124. https://doi.org/10.1016/j.cell.2007.11.042
Hsu EC, Kulp SK, Huang HL, Tu HJ, Salunke SB, Sullivan NJ, Sun D, Wicha MS, Shapiro CL, Chen CS (2015) Function of integrin-linked kinase in modulating the stemness of IL-6-abundant breast cancer cells by regulating γ-secretase-mediated Notch1 activation in caveolae. Neoplasia 17(6):497–508. https://doi.org/10.1016/j.neo.2015.06.001
Jang I, Beningo KA (2019) Integrins CAFs and mechanical forces in the progression of cancer. Cancers. https://doi.org/10.3390/cancers11050721
Jasmin JF, Yang M, Iacovitti L, Lisanti MP (2009) Genetic ablation of caveolin-1 increases neural stem cell proliferation in the subventricular zone (SVZ) of the adult mouse brain. Cell Cycle 8(23):3978–3983. https://doi.org/10.4161/cc.8.23.10206
Jayaramayya K, Mahalaxmi I, Subramaniam MD, Raj N, Dayem AA, Lim KM, Kim SJ, An JY, Lee Y, Choi Y, Raj A, Cho SG, Vellingiri B (2020) Immunomodulatory effect of mesenchymal stem cells and mesenchymal stem-cell-derived exosomes for COVID-19 treatment. BMB Rep 53(8):400–412. https://doi.org/10.5483/BMBRep.2020.53.8.121
Kaler J, Hussain A, Haque A, Naveed H, Patel S (2020) A comprehensive review of pharmaceutical and surgical interventions of prostate cancer. Cureus 12(11):e11617. https://doi.org/10.7759/cureus.11617
Kalluri R, LeBleu VS (2020) The biology, function, and biomedical applications of exosomes. Science. https://doi.org/10.1126/science.aau6977
Kaushik K, Das A (2019) Endothelial progenitor cell therapy for chronic wound tissue regeneration. Cytotherapy 21(11):1137–1150. https://doi.org/10.1016/j.jcyt.2019.09.002
Khaddour K, Hana CK, Mewawalla P (2020) Hematopoietic stem cell transplantation. StatPearls Publishing LLC, Treasure Island
Kim YJ, Kim JH, Kim O, Ahn EJ, Oh SJ, Akanda MR, Oh IJ, Jung S, Kim KK, Lee JH, Kim HS, Kim H, Lee KH, Moon KS (2019) Caveolin-1 enhances brain metastasis of non-small cell lung cancer, potentially in association with the epithelial-mesenchymal transition marker SNAIL. Cancer Cell Int 19:171. https://doi.org/10.1186/s12935-019-0892-0
Kobayashi T, Kageyama R (2020) Lysosomes and signaling pathways for maintenance of quiescence in adult neural stem cells. FEBS J. https://doi.org/10.1111/febs.15555
Kocaadam B, Şanlier N (2017) Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. Crit Rev Food Sci Nutr 57(13):2889–2895. https://doi.org/10.1080/10408398.2015.1077195
Kou X, Xu X, Chen C, Sanmillan ML, Cai T, Zhou Y, Giraudo C, Le A, Shi S (2018) The Fas/Fap-1/Cav-1 complex regulates IL-1RA secretion in mesenchymal stem cells to accelerate wound healing. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aai8524
Kovtun O, Tillu VA, Ariotti N, Parton RG, Collins BM (2015) Cavin family proteins and the assembly of caveolae. J Cell Sci 128(7):1269–1278. https://doi.org/10.1242/jcs.167866
Lajoie P, Nabi IR (2010) Lipid rafts, caveolae, and their endocytosis. Int Rev Cell Mol Biol 282:135–163. https://doi.org/10.1016/s1937-6448(10)82003-9
Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648. https://doi.org/10.1038/367645a0
Lee MY, Lee SH, Park JH, Han HJ (2009) Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways. Cell Mol Life Sci 66(8):1467–1478. https://doi.org/10.1007/s00018-009-8691-8
Lee MY, Ryu JM, Lee SH, Park JH, Han HJ (2010) Lipid rafts play an important role for maintenance of embryonic stem cell self-renewal. J Lipid Res 51(8):2082–2089. https://doi.org/10.1194/jlr.M001545
Lee SH, Lee YJ, Park SW, Kim HS, Han HJ (2011) Caveolin-1 and integrin β1 regulate embryonic stem cell proliferation via p38 MAPK and FAK in high glucose. J Cell Physiol 226(7):1850–1859. https://doi.org/10.1002/jcp.22510
Lee E, Piranlioglu R, Wicha MS, Korkaya H (2019) Plasticity and potency of mammary stem cell subsets during mammary gland development. Int J Mol Sci. https://doi.org/10.3390/ijms20092357
Li J, Hassan GS, Williams TM, Minetti C, Pestell RG, Tanowitz HB, Frank PG, Sotgia F, Lisanti MP (2005) Loss of caveolin-1 causes the hyper-proliferation of intestinal crypt stem cells, with increased sensitivity to whole body gamma-radiation. Cell Cycle 4(12):1817–1825. https://doi.org/10.4161/cc.4.12.2199
Li Y, Lau WM, So KF, Tong Y, Shen J (2011a) Caveolin-1 promote astroglial differentiation of neural stem/progenitor cells through modulating Notch1/NICD and Hes1 expressions. Biochem Biophys Res Commun 407(3):517–524. https://doi.org/10.1016/j.bbrc.2011.03.050
Li Y, Lau WM, So KF, Tong Y, Shen J (2011b) Caveolin-1 inhibits oligodendroglial differentiation of neural stem/progenitor cells through modulating β-catenin expression. Neurochem Int 59(2):114–121. https://doi.org/10.1016/j.neuint.2011.05.019
Li Y, Luo J, Lau WM, Zheng G, Fu S, Wang TT, Zeng HP, So KF, Chung SK, Tong Y, Liu K, Shen J (2011c) Caveolin-1 plays a crucial role in inhibiting neuronal differentiation of neural stem/progenitor cells via VEGF signaling-dependent pathway. PLoS ONE 6(8):e22901. https://doi.org/10.1371/journal.pone.0022901
Li Y, Zhao Y, Gao C, Wu M, So KF, Tong Y, Shen J (2020) Caveolin-1 derived from brain microvascular endothelial cells inhibits neuronal differentiation of neural stem/progenitor cells in vivo and in vitro. Neuroscience 448:172–190. https://doi.org/10.1016/j.neuroscience.2020.09.031
Lin CJ, Yun EJ, Lo UG, Tai YL, Deng S, Hernandez E, Dang A, Chen YA, Saha D, Mu P, Lin H, Li TK, Shen TL, Lai CH, Hsieh JT (2019) The paracrine induction of prostate cancer progression by caveolin-1. Cell Death Dis 10(11):834. https://doi.org/10.1038/s41419-019-2066-3
Liu YC, Yeh CT, Lin KH (2020a) Cancer stem cell functions in hepatocellular carcinoma and comprehensive therapeutic strategies. Cells. https://doi.org/10.3390/cells9061331
Liu Y, Fu Y, Hu X, Chen S, Miao J, Wang Y, Zhou Y, Zhang Y (2020b) Caveolin-1 knockdown increases the therapeutic sensitivity of lung cancer to cisplatin-induced apoptosis by repressing Parkin-related mitophagy and activating the ROCK1 pathway. J Cell Physiol 235(2):1197–1208. https://doi.org/10.1002/jcp.29033
Luanpitpong S, Wang L, Stueckle TA, Tse W, Chen YC, Rojanasakul Y (2014) Caveolin-1 regulates lung cancer stem-like cell induction and p53 inactivation in carbon nanotube-driven tumorigenesis. Oncotarget 5(11):3541–3554. https://doi.org/10.18632/oncotarget.1956
Ly CH, Lynch GS, Ryall JG (2020) A metabolic roadmap for somatic stem cell fate. Cell Metab 31(6):1052–1067. https://doi.org/10.1016/j.cmet.2020.04.022
Ma ZJ, Yang JJ, Lu YB, Liu ZY, Wang XX (2020) Mesenchymal stem cell-derived exosomes: toward cell-free therapeutic strategies in regenerative medicine. World J Stem Cells 12(8):814–840. https://doi.org/10.4252/wjsc.v12.i8.814
Maiuthed A, Bhummaphan N, Luanpitpong S, Mutirangura A, Aporntewan C, Meeprasert A, Rungrotmongkol T, Rojanasakul Y, Chanvorachote P (2018) Nitric oxide promotes cancer cell dedifferentiation by disrupting an Oct4:caveolin-1 complex: a new regulatory mechanism for cancer stem cell formation. J Biol Chem 293(35):13534–13552. https://doi.org/10.1074/jbc.RA117.000287
Makdissy N, Haddad K, AlBacha JD, Chaker D, Ismail B, Azar A, Oreibi G, Ayoub D, Achkar I, Quilliot D, Fajloun Z (2018) Essential role of ATP6AP2 enrichment in caveolae/lipid raft microdomains for the induction of neuronal differentiation of stem cells. Stem Cell Res Ther 9(1):132. https://doi.org/10.1186/s13287-018-0862-9
Margheri F, Chillà A, Laurenzana A, Serratì S, Mazzanti B, Saccardi R, Santosuosso M, Danza G, Sturli N, Rosati F, Magnelli L, Papucci L, Calorini L, Bianchini F, Del Rosso M, Fibbi G (2011) Endothelial progenitor cell-dependent angiogenesis requires localization of the full-length form of uPAR in caveolae. Blood 118(13):3743–3755. https://doi.org/10.1182/blood-2011-02-338681
Martínez-Cerdeño V, Noctor SC (2018) Neural progenitor cell terminology. Front Neuroanat 12:104. https://doi.org/10.3389/fnana.2018.00104
Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, Chiavarina B, Migneco G, Witkiewicz AK, Martinez-Cantarin MP, Flomenberg N, Howell A, Pestell RG, Lisanti MP, Sotgia F (2010) Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle 9(12):2423–2433. https://doi.org/10.4161/cc.9.12.12048
Mathews LA, Cabarcas SM, Farrar WL (2011) DNA repair: the culprit for tumor-initiating cell survival? Cancer Metastasis Rev 30(2):185–197. https://doi.org/10.1007/s10555-011-9277-0
Megaloikonomos PD, Panagopoulos GN, Bami M, Igoumenou VG, Dimopoulos L, Milonaki A, Kyriakidou M, Mitsiokapa E, Anastassopoulou J, Mavrogenis AF (2018) Harvesting, isolation and differentiation of rat adipose-derived stem cells. Curr Pharm Biotechnol 19(1):19–29. https://doi.org/10.2174/1389201019666180418101323
Nassoy P, Lamaze C (2012) Stressing caveolae new role in cell mechanics. Trends Cell Biol 22(7):381–389. https://doi.org/10.1016/j.tcb.2012.04.007
Nimmakayala RK, Batra SK, Ponnusamy MP (2019) Unraveling the journey of cancer stem cells from origin to metastasis. Biochim Biophys Acta Rev Cancer 1871(1):50–63. https://doi.org/10.1016/j.bbcan.2018.10.006
Nogueira ML, da Veiga MJ, Baronzio GF, Dubois B, Steyaert JM, Schwartz L (2015) Mechanical stress as the common denominator between chronic inflammation, cancer, and Alzheimer’s disease. Front Oncol 5:197. https://doi.org/10.3389/fonc.2015.00197
Olbromski M, Podhorska-Okołów M, Dzięgiel P (2020) Role of SOX protein groups F and H in lung cancer progression. Cancers. https://doi.org/10.3390/cancers12113235
Othman FA, Tan SC (2020) Preconditioning strategies to enhance neural stem cell-based therapy for ischemic stroke. Brain Sci. https://doi.org/10.3390/brainsci10110893
Park JH, Han HJ (2009) Caveolin-1 plays important role in EGF-induced migration and proliferation of mouse embryonic stem cells: involvement of PI3K/Akt and ERK. Am J Physiol Cell Physiol 297(4):C935-944. https://doi.org/10.1152/ajpcell.00121.2009
Park JS, Kim HY, Kim HW, Chae GN, Oh HT, Park JY, Shim H, Seo M, Shin EY, Kim EG, Park SC, Kwak SJ (2005) Increased caveolin-1, a cause for the declined adipogenic potential of senescent human mesenchymal stem cells. Mech Ageing Dev 126(5):551–559. https://doi.org/10.1016/j.mad.2004.11.014
Park JH, Lee MY, Han HJ (2009) A potential role for caveolin-1 in estradiol-17beta-induced proliferation of mouse embryonic stem cells: involvement of Src, PI3K/Akt, and MAPKs pathways. Int J Biochem Cell Biol 41(3):659–665. https://doi.org/10.1016/j.biocel.2008.07.010
Park JH, Ryu JM, Han HJ (2011) Involvement of caveolin-1 in fibronectin-induced mouse embryonic stem cell proliferation: role of FAK, RhoA, PI3K/Akt, and ERK 1/2 pathways. J Cell Physiol 226(1):267–275. https://doi.org/10.1002/jcp.22338
Park JH, Ryu JM, Yun SP, Kim MO, Han HJ (2012) Fibronectin stimulates migration through lipid raft dependent NHE-1 activation in mouse embryonic stem cells: involvement of RhoA, Ca(2+)/CaM, and ERK. Biochim Biophys Acta 1820(10):1618–1627. https://doi.org/10.1016/j.bbagen.2012.05.013
Patel HH, Murray F, Insel PA (2008) Caveolae as organizers of pharmacologically relevant signal transduction molecules. Annu Rev Pharmacol Toxicol 48:359–391. https://doi.org/10.1146/annurev.pharmtox.48.121506.124841
Paternoster S, Falasca M (2020) The intricate relationship between diabetes, obesity and pancreatic cancer. Biochim Biophys Acta Rev Cancer 1873(1):188326. https://doi.org/10.1016/j.bbcan.2019.188326
Peffer ME, Chandran UR, Luthra S, Volonte D, Galbiati F, Garabedian MJ, Monaghan AP, DeFranco DB (2014) Caveolin-1 regulates genomic action of the glucocorticoid receptor in neural stem cells. Mol Cell Biol 34(14):2611–2623. https://doi.org/10.1128/mcb.01121-13
Phiboonchaiyanan PP, Kiratipaiboon C, Chanvorachote P (2016) Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. Chem Biol Interact 250:1–11. https://doi.org/10.1016/j.cbi.2016.03.005
Qian XL, Pan YH, Huang QY, Shi YB, Huang QY, Hu ZZ, Xiong LX (2019) Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment. Onco Targets Ther 12:1539–1552. https://doi.org/10.2147/ott.s191317
Qin W, Zheng Y, Qian BZ, Zhao M (2017) Prostate cancer stem cells and nanotechnology: a focus on Wnt signaling. Front Pharmacol 8:153. https://doi.org/10.3389/fphar.2017.00153
Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19(11):1423–1437. https://doi.org/10.1038/nm.3394
Ramazzotti G, Ratti S, Fiume R, Follo MY, Billi AM, Rusciano I, Obeng EO, Manzoli L, Cocco L, Faenza I (2019) Phosphoinositide 3 kinase signaling in human stem cells from reprogramming to differentiation: a tale in cytoplasmic and nuclear compartments. Int J Mol Sci. https://doi.org/10.3390/ijms20082026
Rebuzzini P, Zuccotti M, Redi CA, Garagna S (2015) Chromosomal abnormalities in embryonic and somatic stem cells. Cytogenet Genome Res 147(1):1–9. https://doi.org/10.1159/000441645
Ren M, Liu F, Zhu Y, Li Y, Lang R, Fan Y, Gu F, Zhang X, Fu L (2014) Absence of caveolin-1 expression in carcinoma-associated fibroblasts of invasive micropapillary carcinoma of the breast predicts poor patient outcome. Virchows Arch 465(3):291–298. https://doi.org/10.1007/s00428-014-1614-6
Ren K, Tang J, Jiang X, Sun H, Nong L, Shen N, Gu Y (2018) Periodic mechanical stress stimulates Cav-1-dependent IGF-1R mitogenic signals in rat chondrocytes through ERK1/2. Cell Physiol Biochem 48(4):1652–1663. https://doi.org/10.1159/000492288
Rigaud VOC, Hoy R, Mohsin S, Khan M (2020) Stem cell metabolism: powering cell-based therapeutics. Cells. https://doi.org/10.3390/cells9112490
Rivera C, Rivera S, Loriot Y, Vozenin MC, Deutsch E (2011) Lung cancer stem cell: new insights on experimental models and preclinical data. J Oncol 2011:549181. https://doi.org/10.1155/2011/549181
Rodrigues M, Kosaric N, Bonham CA, Gurtner GC (2019) Wound healing: a cellular perspective. Physiol Rev 99(1):665–706. https://doi.org/10.1152/physrev.00067.2017
Romeo F, Costanzo F, Agostini M (2012) Embryonic stem cells and inducible pluripotent stem cells: two faces of the same coin? Aging 4(12):878–886. https://doi.org/10.18632/aging.100513
Root KT, Plucinsky SM, Glover KJ (2015) Recent progress in the topology, structure, and oligomerization of caveolin: a building block of caveolae. Curr Top Membr 75:305–336. https://doi.org/10.1016/bs.ctm.2015.03.007
Rycaj K, Tang DG (2015) Cell-of-origin of cancer versus cancer stem cells: assays and interpretations. Cancer Res 75(19):4003–4011. https://doi.org/10.1158/0008-5472.can-15-0798
Sasaki N, Shinomi M, Hirano K, Ui-Tei K, Nishihara S (2011) LacdiNAc (GalNAcβ1-4GlcNAc) contributes to self-renewal of mouse embryonic stem cells by regulating leukemia inhibitory factor/STAT3 signaling. Stem Cells 29(4):641–650. https://doi.org/10.1002/stem.615
Semba T, Sammons R, Wang X, Xie X, Dalby KN, Ueno NT (2020) JNK signaling in stem cell self-renewal and differentiation. Int J Mol Sci. https://doi.org/10.3390/ijms21072613
Shan-Wei W, Kan-Lun X, Shu-Qin R, Li-Li Z, Li-Rong C (2012) Overexpression of caveolin-1 in cancer-associated fibroblasts predicts good outcome in breast cancer. Breast Care 7(6):477–483. https://doi.org/10.1159/000345464
Shi XY, Xiong LX, Xiao L, Meng C, Qi GY, Li WL (2016) Downregulation of caveolin-1 upregulates the expression of growth factors and regulators in co-culture of fibroblasts with cancer cells. Mol Med Rep 13(1):744–752. https://doi.org/10.3892/mmr.2015.4610
Shimizu K, Chiba S, Hori Y (2013) Identification of a novel subpopulation of tumor-initiating cells from gemcitabine-resistant pancreatic ductal adenocarcinoma patients. PLoS ONE 8(11):e81283. https://doi.org/10.1371/journal.pone.0081283
Siegel RL, Miller KD, Jemal A (2020) Cancer statistics. CA Cancer J Clin 70(1):7–30. https://doi.org/10.3322/caac.21590
Simón L, Campos A, Leyton L, Quest AFG (2020) Caveolin-1 function at the plasma membrane and in intracellular compartments in cancer. Cancer Metastasis Rev 39(2):435–453. https://doi.org/10.1007/s10555-020-09890-x
Singh V, Lamaze C (2020) Membrane tension buffering by caveolae: a role in cancer? Cancer Metastasis Rev 39(2):505–517. https://doi.org/10.1007/s10555-020-09899-2
Sinha B, Köster D, Ruez R, Gonnord P, Bastiani M, Abankwa D, Stan RV, Butler-Browne G, Vedie B, Johannes L, Morone N, Parton RG, Raposo G, Sens P, Lamaze C, Nassoy P (2011) Cells respond to mechanical stress by rapid disassembly of caveolae. Cell 144(3):402–413. https://doi.org/10.1016/j.cell.2010.12.031
Skotland T, Kavaliauskiene S, Sandvig K (2020) The role of lipid species in membranes and cancer-related changes. Cancer Metastasis Rev 39(2):343–360. https://doi.org/10.1007/s10555-020-09872-z
Soleimani F, Babaei E, Feizi MAH, Fathi F (2020) CRISPR-Cas9-mediated knockout of the Prkdc in mouse embryonic stem cells leads to the modulation of the expression of pluripotency genes. J Cell Physiol 235(4):3994–4000. https://doi.org/10.1002/jcp.29295
Soman SS, Vijayavenkataraman S (2020) Applications of 3D bioprinted-induced pluripotent stem cells in healthcare. Int J Bioprint 6(4):280. https://doi.org/10.18063/ijb.v6i4.280
Sotgia F, Williams TM, Cohen AW, Minetti C, Pestell RG, Lisanti MP (2005) Caveolin-1-deficient mice have an increased mammary stem cell population with upregulation of Wnt/beta-catenin signaling. Cell Cycle 4(12):1808–1816. https://doi.org/10.4161/cc.4.12.2198
Spill F, Reynolds DS, Kamm RD, Zaman MH (2016) Impact of the physical microenvironment on tumor progression and metastasis. Curr Opin Biotechnol 40:41–48. https://doi.org/10.1016/j.copbio.2016.02.007
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676. https://doi.org/10.1016/j.cell.2006.07.024
Tan Z, Zhou LJ, Li Y, Cui YH, Xiang QL, Lin GP, Wang TH (2012) E2-BSA activates caveolin-1 via PI3K/ERK1/2 and lysosomal degradation pathway and contributes to EPC proliferation. Int J Cardiol 158(1):46–53. https://doi.org/10.1016/j.ijcard.2010.12.106
Teng F, Fussenegger M (2020) Shedding light on extracellular vesicle biogenesis and bioengineering. Adv Sci 8(1):2003505. https://doi.org/10.1002/advs.202003505
Teo JL, Gomez GA, Weeratunga S, Davies EM, Noordstra I, Budnar S, Katsuno-Kambe H, McGrath MJ, Verma S, Tomatis V, Acharya BR, Balasubramaniam L, Templin RM, McMahon KA, Lee YS, Ju RJ, Stebhens SJ, Ladoux B, Mitchell CA, Collins BM, Parton RG, Yap AS (2020) Caveolae control contractile tension for epithelia to eliminate tumor cells. Dev Cell 54(1):75-91.e77. https://doi.org/10.1016/j.devcel.2020.05.002
Testa U, Castelli G, Pelosi E (2020) Breast cancer: a molecularly heterogenous disease needing subtype-specific treatments. Med Sci. https://doi.org/10.3390/medsci8010018
Thankamony AP, Saxena K, Murali R, Jolly MK, Nair R (2020) Cancer stem cell plasticity—a deadly deal. Front Mol Biosci 7:79. https://doi.org/10.3389/fmolb.2020.00079
Tweedell KS (2017) The adaptability of somatic stem cells: a review. J Stem Cells Regener Med 13(1):3–13. https://doi.org/10.46582/jsrm.1301002
Urueña C, Sandoval TA, Lasso P, Tawil M, Barreto A, Torregrosa L, Fiorentino S (2020) Evaluation of chemotherapy and P2Et extract combination in ex-vivo derived tumor mammospheres from breast cancer patients. Sci Rep 10(1):19639. https://doi.org/10.1038/s41598-020-76619-9
Vainonen JP, Aboulaich N, Turkina MV, Strålfors P, Vener AV (2004) N-terminal processing and modifications of caveolin-1 in caveolae from human adipocytes. Biochem Biophys Res Commun 320(2):480–486. https://doi.org/10.1016/j.bbrc.2004.05.196
Visvader JE (2011) Cells of origin in cancer. Nature 469(7330):314–322. https://doi.org/10.1038/nature09781
Volonte D, Vyas AR, Chen C, Dacic S, Stabile LP, Kurland BF, Abberbock SR, Burns TF, Herman JG, Di YP, Galbiati F (2018) Caveolin-1 promotes the tumor suppressor properties of oncogene-induced cellular senescence. J Biol Chem 293(5):1794–1809. https://doi.org/10.1074/jbc.M117.815902
Wang S, Kan Q, Sun Y, Han R, Zhang G, Peng T, Jia Y (2013) Caveolin-1 regulates neural differentiation of rat bone mesenchymal stem cells into neurons by modulating notch signaling. Int J Dev Neurosci 31(1):30–35. https://doi.org/10.1016/j.ijdevneu.2012.09.004
Wang Z, Wang N, Li W, Liu P, Chen Q, Situ H, Zhong S, Guo L, Lin Y, Shen J, Chen J (2014a) Caveolin-1 mediates chemoresistance in breast cancer stem cells via β-catenin/ABCG2 signaling pathway. Carcinogenesis 35(10):2346–2356. https://doi.org/10.1093/carcin/bgu155
Wang J, Li ZH, White J, Zhang LB (2014b) Lung cancer stem cells and implications for future therapeutics. Cell Biochem Biophys 69(3):389–398. https://doi.org/10.1007/s12013-014-9844-4
Wang R, Li Z, Guo H, Shi W, Xin Y, Chang W, Huang T (2014c) Caveolin 1 knockdown inhibits the proliferation, migration and invasion of human breast cancer BT474 cells. Mol Med Rep 9(5):1723–1728. https://doi.org/10.3892/mmr.2014.2018
Wang D, Bu F, Zhang W (2019a) The role of ubiquitination in regulating embryonic stem cell maintenance and cancer development. Int J Mol Sci. https://doi.org/10.3390/ijms20112667
Wang S, Zhang Z, Almenar-Queralt A, Leem J, DerMardirossian C, Roth DM, Patel PM, Patel HH, Head BP (2019b) Caveolin-1 phosphorylation is essential for axonal growth of human neurons derived from iPSCs. Front Cell Neurosci 13:324. https://doi.org/10.3389/fncel.2019.00324
Wang Y, Jiang Z, Yu M, Yang G (2020a) Roles of circular RNAs in regulating the self-renewal and differentiation of adult stem cells. Differentiation 113:10–18. https://doi.org/10.1016/j.diff.2020.03.001
Wang S, Wang N, Zheng Y, Yang B, Liu P, Zhang F, Li M, Song J, Chang X, Wang Z (2020b) Caveolin-1 inhibits breast cancer stem cells via c-Myc-mediated metabolic reprogramming. Cell Death Dis 11(6):450. https://doi.org/10.1038/s41419-020-2667-x
Williams TM, Lisanti MP (2004) The caveolin proteins. Genome Biol 5(3):214. https://doi.org/10.1186/gb-2004-5-3-214
Williams TM, Lisanti MP (2005) Caveolin-1 in oncogenic transformation, cancer, and metastasis. Am J Physiol Cell Physiol 288(3):C494-506. https://doi.org/10.1152/ajpcell.00458.2004
Wong TH, Dickson FH, Timmins LR, Nabi IR (2020) Tyrosine phosphorylation of tumor cell caveolin-1: impact on cancer progression. Cancer Metastasis Rev 39(2):455–469. https://doi.org/10.1007/s10555-020-09892-9
Yadav P, Vats R, Bano A, Bhardwaj R (2020) Hematopoietic stem cells culture, expansion and differentiation: an insight into variable and available media. Int J Stem Cells. https://doi.org/10.15283/ijsc19157
Yamaguchi T, Lu C, Ida L, Yanagisawa K, Usukura J, Cheng J, Hotta N, Shimada Y, Isomura H, Suzuki M, Fujimoto T, Takahashi T (2016) ROR1 sustains caveolae and survival signalling as a scaffold of cavin-1 and caveolin-1. Nat Commun 7:10060. https://doi.org/10.1038/ncomms10060
Yan F, Su L, Chen X, Wang X, Gao H, Zeng Y (2020) Molecular regulation and clinical significance of caveolin-1 methylation in chronic lung diseases. Clin Transl Med 10(1):151–160. https://doi.org/10.1002/ctm2.2
Yanagisawa M, Yu RK (2007) The expression and functions of glycoconjugates in neural stem cells. Glycobiology 17(7):57r–74r. https://doi.org/10.1093/glycob/cwm018
Yang R, Liu F, Wang J, Chen X, Xie J, Xiong K (2019a) Epidermal stem cells in wound healing and their clinical applications. Stem Cell Res Ther 10(1):229. https://doi.org/10.1186/s13287-019-1312-z
Yang R, Wang J, Zhou Z, Qi S, Ruan S, Lin Z, Xin Q, Lin Y, Chen X, Xie J (2019b) Role of caveolin-1 in epidermal stem cells during burn wound healing in rats. Dev Biol 445(2):271–279. https://doi.org/10.1016/j.ydbio.2018.11.015
Yang R, Wang J, Zhou Z, Qi S, Ruan S, Lin Z, Xin Q, Lin Y, Chen X, Xie J (2019c) Curcumin promotes burn wound healing in mice by upregulating caveolin-1 in epidermal stem cells. Phytother Res 33(2):422–430. https://doi.org/10.1002/ptr.6238
Yang C, He B, Dai W, Zhang H, Zheng Y, Wang X, Zhang Q (2021) The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems. Acta Pharm Sin B 11(4):961–977. https://doi.org/10.1016/j.apsb.2020.11.020
Yongsanguanchai N, Pongrakhananon V, Mutirangura A, Rojanasakul Y, Chanvorachote P (2015) Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells. Am J Physiol Cell Physiol 308(2):C89-100. https://doi.org/10.1152/ajpcell.00187.2014
Yun SP, Ryu JM, Kim MO, Park JH, Han HJ (2012) Rapid actions of plasma membrane estrogen receptors regulate motility of mouse embryonic stem cells through a profilin-1/cofilin-1-directed kinase signaling pathway. Mol Endocrinol 26(8):1291–1303. https://doi.org/10.1210/me.2012-1002
Yun SP, Lee SJ, Jung YH, Han HJ (2014) Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent collagen 3/5 and upregulation of NF-κB-dependent fibronectin/laminin 5 expression. Cell Death Dis 5(2):e1049. https://doi.org/10.1038/cddis.2014.3
Zanotti S, Canalis E (2016) Notch signaling and the skeleton. Endocr Rev 37(3):223–253. https://doi.org/10.1210/er.2016-1002
Zhai L, Liu Y, Zhao W, Chen Q, Guo T, Wei W, Luo Z, Huang Y, Ma C, Huang F, Dai X (2020) Aerobic and resistance training enhances endothelial progenitor cell function via upregulation of caveolin-1 in mice with type 2 diabetes. Stem Cell Res Ther 11(1):10. https://doi.org/10.1186/s13287-019-1527-z
Zhao Y, Pang Q, Liu M, Pan J, Xiang B, Huang T, Tu F, Liu C, Chen X (2017) Treadmill exercise promotes neurogenesis in ischemic rat brains via caveolin-1/VEGF signaling pathways. Neurochem Res 42(2):389–397. https://doi.org/10.1007/s11064-016-2081-z
Zheng W, Li J, Wang X, Yuan Y, Zhang J, Xiu Z (2018) Effects of Antarctic krill docosahexaenoic acid on MCF-7 cell migration and invasion induced by the interaction of CD95 with caveolin-1. Life Sci 192:270–277. https://doi.org/10.1016/j.lfs.2017.11.011
Zhu J, Wang S, Chen Y, Li X, Jiang Y, Yang X, Li Y, Wang X, Meng Y, Zhu M, Ma X, Huang C, Wu R, Xie C, Geng S, Wu J, Zhong C, Han H (2017) miR-19 targeting of GSK3β mediates sulforaphane suppression of lung cancer stem cells. J Nutr Biochem 44:80–91. https://doi.org/10.1016/j.jnutbio.2017.02.020
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We would like to thank the English editing support by Wanting Yi and Yubo Shi.
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This work was supported by the National Natural Science Foundation of China, Major Research Plan (NSFC No. 31860317) and the National natural science foundation of Jiangxi province (No. 20202BAB206056), as well as the college students innovation training program of Nanchang University (No. 20190402024, No. 20190402025).
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Lai, X., Guo, Y., Chen, M. et al. Caveolin1: its roles in normal and cancer stem cells. J Cancer Res Clin Oncol 147, 3459–3475 (2021). https://doi.org/10.1007/s00432-021-03793-2
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DOI: https://doi.org/10.1007/s00432-021-03793-2