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Extracellular-matrix mechanics regulate cellular metabolism: A ninja warrior behind mechano-chemo signaling crosstalk

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Abstract

Mechanical forces are the indispensable constituent of environmental cues, such as gravity, barometric pressure, vibration, and contact with bodies, which are involved in pattern and organogenesis, providing mechanical input to tissues and determining the ultimate fate of cells. Extracellular matrix (ECM) stiffness, the slow elastic force, carries the external physical force load onto the cell or outputs the internal force exerted by the cell and its neighbors into the environment. Accumulating evidence illustrates the pivotal role of ECM stiffness in the regulation of organogenesis, maintenance of tissue homeostasis, and the development of multiple diseases, which is largely fulfilled through its systematical impact on cellular metabolism. This review summarizes the establishment and regulation of ECM stiffness, the mechanisms underlying how ECM stiffness is sensed by cells and signals to modulate diverse cell metabolic pathways, and the physiological and pathological significance of the ECM stiffness-cell metabolism axis.

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Abbreviations

ECM:

Extracellular matrix

YAP/TAZ:

Yes-associated protein/transcriptional coactivator with pdz-binding motif

PDAC:

Pancreatic ductal carcinoma

MMPs:

Matrix metalloproteinases

LINC:

Linker of nucleoskeleton and cytoskeleton

KASH domain:

Klarsicht, anc-1, syne homology domain

FAK:

Focal adhesion kinase

ROCK:

Rho-associated protein kinase

CAS:

Crk-associated substrate

MLC:

Myosin light chain

MAPK:

Mitogen-activated protein kinase

ERK:

Extracellular signal-regulated kinase

TRPV4:

Transient receptor potential vanilloid 4

TGFβ1:

Transforming growth factor β1

EMT:

Epithelial-mesenchymal transition

CaM:

Calmodulin

NFAT:

Nuclear factor of activated T cells

P5C:

Pyrroline-5-carboxylate

PYCR1:

Pyrroline-5-carboxylate reductase 1

HK1/2:

Hexokinase 1/2

ENO1/2:

Enolase 1/2

ALDO:

Aldolase

DCs:

Dendritic cells

PC:

Pyruvate carboxylase

peroxisome PGC1α:

Proliferator-activated receptor gamma coactivator 1

PCK1:

Phosphoenolpyruvate carboxykinase 1

JNK:

C-jun NH2-terminal kinase

G6PC:

Glucose-6-phosphatase catalytic

GLUT:

Glucose transporter

HCC:

Hepatocellular carcinoma cell

HA:

Hyaluronic acid

SREBP:

Sterol regulatory element binding protein

ARF1:

ADP ribosylation factor 1

12-LOX:

12-Lipoxygenase

AMPK:

Amp-activated protein kinase

SCD-1:

Stearoyl-CoA desaturase 1

ACL:

ATP citrate lyase

FAS:

Fatty acid synthasel

ACC1:

Acetyl-CoA carboxylase 1

HMGCR:

3-Hydroxy-3-methylglutaryl-CoA reductase

LDLR:

Low density lipoprotein

MSC:

Mesenchymal stem cell

PPP:

Pentose phosphate pathway

LATS1/2:

Large tumor suppressor kinase 1/2

PRPS:

Phosphoribosyl pyrophosphate synthetase

TRAF2:

TNF receptor-associated factor 2

RNR:

Ribonucleotide reductase

TYMS:

Thymidylate synthase

DTYMK:

Deoxythymidylate kinase

TK1:

Thymidine kinase

VSMC:

Vascular smooth muscle cell

DNMT1:

DNA methyltransferase 1

References

  1. Guo CL, Harris NC, Wijeratne SS, et al. Multiscale mechanobiology: Mechanics at the molecular, cellular, and tissue levels. Cell Biosci. 2013;3.

  2. Geiger B, Spatz JP, Bershadsky AD. Environmental sensing through focal adhesions. Nat Rev Mol Cell Bio. 2009;10(1):21–33.

    Article  CAS  Google Scholar 

  3. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15(12):786–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Romani P, Valcarcel-Jimenez L, Frezza C, et al. Crosstalk between mechanotransduction and metabolism. Nat Rev Mol Cell Biol. 2021;22(1):22–38.

    Article  CAS  PubMed  Google Scholar 

  5. Martino F, Perestrelo AR, Vinarsky V, et al. Cellular Mechanotransduction: From Tension to Function. Front Physiol. 2018;9:824.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Darling EM, Di Carlo D. High-Throughput Assessment of Cellular Mechanical Properties. Annu Rev Biomed Eng. 2015;17:35–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pinheiro D, Bellaiche Y. Mechanical Force-Driven Adherens Junction Remodeling and Epithelial Dynamics. Dev Cell. 2018;47(1):3–19.

    Article  CAS  PubMed  Google Scholar 

  8. Kai F, Laklai H, Weaver VM. Force Matters: Biomechanical Regulation of Cell Invasion and Migration in Disease. Trends Cell Biol. 2016;26(7):486–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sun M, Chi G, Xu J, et al. Extracellular matrix stiffness controls osteogenic differentiation of mesenchymal stem cells mediated by integrin alpha5. Stem Cell Res Ther. 2018;9(1):52.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhang W, Zhang S, Zhang W, et al. Matrix stiffness and its influence on pancreatic diseases. Biochim Biophys Acta Rev Cancer. 2021;1876(1):188583.

    Article  CAS  PubMed  Google Scholar 

  11. Seewaldt V. ECM stiffness paves the way for tumor cells. Nat Med. 2014;20(4):332–3.

    Article  CAS  PubMed  Google Scholar 

  12. Piersma B, Hayward MK, Weaver VM. Fibrosis and cancer: A strained relationship. Biochim Biophys Acta Rev Cancer. 2020;1873(2):188356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Upagupta C, Shimbori C, Alsilmi R, et al. Matrix abnormalities in pulmonary fibrosis. Eur Respir Rev. 2018;27(148).

  14. Vignes H, Vagena-Pantoula C, Vermot J. Mechanical control of tissue shape: Cell-extrinsic and -intrinsic mechanisms join forces to regulate morphogenesis. Semin Cell Dev Biol. 2022.

  15. Nia HT, Munn LL, Jain RK. Physical traits of cancer. Science. 2020;370(6516).

  16. Vining KH, Mooney DJ. Mechanical forces direct stem cell behaviour in development and regeneration. Nat Rev Mol Cell Biol. 2017;18(12):728–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Deng M, Lin J, Nowsheen S, et al. Extracellular matrix stiffness determines DNA repair efficiency and cellular sensitivity to genotoxic agents. Sci Adv. 2020;6(37).

  18. Orr AW, Helmke BP, Blackman BR, et al. Mechanisms of mechanotransduction. Dev Cell. 2006;10(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  19. Wang L, You X, Zhang L, et al. Mechanical regulation of bone remodeling. Bone Res. 2022;10(1):16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang N. Review of Cellular Mechanotransduction. J Phys D Appl Phys. 2017;50(23).

  21. Kechagia JZ, Ivaska J, Roca-Cusachs P. Integrins as biomechanical sensors of the microenvironment. Nat Rev Mol Cell Biol. 2019;20(8):457–73.

    Article  CAS  PubMed  Google Scholar 

  22. Sun Z, Guo SS, Fassler R. Integrin-mediated mechanotransduction. J Cell Biol. 2016;215(4):445–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wolfenson H, Yang B, Sheetz MP. Steps in Mechanotransduction Pathways that Control Cell Morphology. Annu Rev Physiol. 2019;81:585–605.

    Article  CAS  PubMed  Google Scholar 

  24. Saini K, Discher DE. Forced Unfolding of Proteins Directs Biochemical Cascades. Biochemistry. 2019;58(49):4893–902.

    Article  CAS  PubMed  Google Scholar 

  25. Humphrey JD, Dufresne ER, Schwartz MA. Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol. 2014;15(12):802–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang B, Ke W, Wang K, et al. Mechanosensitive Ion Channel Piezo1 Activated by Matrix Stiffness Regulates Oxidative Stress-Induced Senescence and Apoptosis in Human Intervertebral Disc Degeneration. Oxid Med Cell Longev. 2021;2021:8884922.

    PubMed  PubMed Central  Google Scholar 

  27. Saotome K, Murthy SE, Kefauver JM, et al. Structure of the mechanically activated ion channel Piezo1. Nature. 2018;554(7693):481–6.

    Article  CAS  PubMed  Google Scholar 

  28. Kefauver JM, Ward AB, Patapoutian A. Discoveries in structure and physiology of mechanically activated ion channels. Nature. 2020;587(7835):567–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kirby TJ, Lammerding J. Emerging views of the nucleus as a cellular mechanosensor. Nat Cell Biol. 2018;20(4):373–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang N, Tytell JDEID. Mechanotransduction at a distance: Mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Bio. 2009;10(1):75–82.

  31. Elosegui-Artola A, Andreu I, Beedle A E M, et al. Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores Cell. 2017;171(6):1397–410 e14.

  32. Bauer MS, Baumann F, Daday C, et al. Structural and mechanistic insights into mechanoactivation of focal adhesion kinase. Proc Natl Acad Sci U S A. 2019;116(14):6766–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Brami-Cherrier K, Gervasi N, Arsenieva D, et al. FAK dimerization controls its kinase-dependent functions at focal adhesions. EMBO J. 2014;33(4):356–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kleinschmidt EG, Schlaepfer DD. Focal adhesion kinase signaling in unexpected places. Curr Opin Cell Biol. 2017;45:24–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: Mechanistic findings and clinical applications. Nat Rev Cancer. 2014;14(9):598–610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sun Z, Costell M, Fassler R. Integrin activation by talin, kindlin and mechanical forces. Nat Cell Biol. 2019;21(1):25–31.

    Article  CAS  PubMed  Google Scholar 

  37. Webb DJ, Donais K, Whitmore LA, et al. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol. 2004;6(2):154–61.

    Article  CAS  PubMed  Google Scholar 

  38. Provenzano PP, Inman DR, Eliceiri KW, et al. Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK-ERK linkage. Oncogene. 2009;28(49):4326–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Shimokawa H, Sunamura S, Satoh K. RhoA/Rho-Kinase in the Cardiovascular System. Circ Res. 2016;118(2):352–66.

    Article  CAS  PubMed  Google Scholar 

  40. Dupont S, Morsut L, Aragona M, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474(7350):179–83.

    Article  CAS  PubMed  Google Scholar 

  41. Nardone G, Oliver-De La Cruz J, Vrbsky J, et al. YAP regulates cell mechanics by controlling focal adhesion assembly. Nat Commun. 2017;8:15321.

  42. Dupont S. Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction. Exp Cell Res. 2016;343(1):42–53.

    Article  CAS  PubMed  Google Scholar 

  43. Hao J, Zhang Y, Wang Y, et al. Role of extracellular matrix and YAP/TAZ in cell fate determination. Cell Signal. 2014;26(2):186–91.

    Article  CAS  PubMed  Google Scholar 

  44. Noguchi S, Saito A, Nagase T. YAP/TAZ Signaling as a Molecular Link between Fibrosis and Cancer. Int J Mol Sci. 2018;19(11).

  45. Totaro A, Castellan M, Battilana G, et al. YAP/TAZ link cell mechanics to Notch signalling to control epidermal stem cell fate. Nat Commun. 2017;8:15206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tang YQ, Lee SA, Rahman M, et al. Ankyrin Is An Intracellular Tether for TMC Mechanotransduction Channels. Neuron. 2020;107(1):112–25 e10.

  47. Dzamba BJ, Jakab KR, Marsden M, et al. Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization. Dev Cell. 2009;16(3):421–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pala R, Alomari N, Nauli SM. Primary Cilium-Dependent Signaling Mechanisms. Int J Mol Sci. 2017;18(11).

  49. Malone AM, Anderson CT, Tummala P, et al. Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism. Proc Natl Acad Sci U S A. 2007;104(33):13325–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Anvarian Z, Mykytyn K, Mukhopadhyay S, et al. Cellular signalling by primary cilia in development, organ function and disease. Nat Rev Nephrol. 2019;15(4):199–219.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Holle AW, Engler AJ. More than a feeling: discovering, understanding, and influencing mechanosensing pathways. Curr Opin Biotech. 2011;22(5):648–54.

    Article  CAS  PubMed  Google Scholar 

  52. Douguet D, Honore E. Mammalian Mechanoelectrical Transduction: Structure and Function of Force-Gated Ion Channels. Cell. 2019;179(2):340–54.

    Article  CAS  PubMed  Google Scholar 

  53. Zhou T, Gao B, Fan Y, et al. Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-ss-catenin. Elife. 2020;9.

  54. Jin P, Jan LY, Jan YN. Mechanosensitive Ion Channels: Structural Features Relevant to Mechanotransduction Mechanisms. Annu Rev Neurosci. 2020;43:207–29.

    Article  CAS  PubMed  Google Scholar 

  55. Karki T, Tojkander S. TRPV Protein Family-From Mechanosensing to Cancer Invasion. Biomolecules. 2021;11(7).

  56. Sharma S, Goswami R, Zhang DX, et al. TRPV4 regulates matrix stiffness and TGFbeta1-induced epithelial-mesenchymal transition. J Cell Mol Med. 2019;23(2):761–74.

    Article  CAS  PubMed  Google Scholar 

  57. COelho NM, Mcculloch CA. Mechanical signaling through the discoidin domain receptor 1 plays a central role in tissue fibrosis. Cell Adh Migr. 2018;12(4):348–62.

  58. Coelho NM, Arora PD, Van Putten S, et al. Discoidin Domain Receptor 1 Mediates Myosin-Dependent Collagen Contraction. Cell Rep. 2017;18(7):1774–90.

    Article  CAS  PubMed  Google Scholar 

  59. Chakraborty M, Chu K, Shrestha A, et al. Mechanical Stiffness Controls Dendritic Cell Metabolism and Function. Cell Rep. 2021;34(2):108609.

    Article  CAS  PubMed  Google Scholar 

  60. Tilghman RW, Blais EM, Cowan CR, et al. Matrix rigidity regulates cancer cell growth by modulating cellular metabolism and protein synthesis. PLoS ONE. 2012;7(5):e37231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hupfer A, Brichkina A, Koeniger A, et al. Matrix stiffness drives stromal autophagy and promotes formation of a protumorigenic niche. Proc Natl Acad Sci USA. 2021;118(40).

  62. Park JS, Burckhardt CJ, Lazcano R, et al. Mechanical regulation of glycolysis via cytoskeleton architecture. Nature. 2020;578(7796):621–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hu H, Juvekar A, Lyssiotis CA, et al. Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton. Cell. 2016;164(3):433–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ge H, Tian M, Pei Q, et al. Extracellular Matrix Stiffness: New Areas Affecting Cell Metabolism. Front Oncol. 2021;11:631991.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Bertero T, Oldham WM, Cottrill KA, et al. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. J Clin Invest. 2016;126(9):3313–35.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Hu Y, Shin DJ, Pan H, et al. YAP suppresses gluconeogenic gene expression through PGC1alpha. Hepatology. 2017;66(6):2029–41.

    Article  CAS  PubMed  Google Scholar 

  67. Liu Q P, Luo Q, Deng B, et al. Stiffer matrix accelerates migration of hepatocellular carcinoma cells through enhanced aerobic glycolysis via the MAPK-YAP signaling. Cancers (Basel). 2020;12(2).

  68. Wang W, Xiao ZD, Li X, et al. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nat Cell Biol. 2015;17(4):490–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Romani P, Brian I, Santinon G, et al. Extracellular matrix mechanical cues regulate lipid metabolism through Lipin-1 and SREBP. Nat Cell Biol. 2019;21(3):338–47.

    Article  CAS  PubMed  Google Scholar 

  70. Bertolio R, Napoletano F, Mano M, et al. Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nat Commun. 2019;10(1):1326.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Yao D, Qiao F, Song C, et al. Matrix stiffness regulates bone repair by modulating 12-lipoxygenase-mediated early inflammation. Mater Sci Eng C Mater Biol Appl. 2021;128: 112359.

    Article  CAS  PubMed  Google Scholar 

  72. Fujisawa K, Takami T, Sasai N, et al. Metabolic alterations in spheroid-cultured hepatic stellate cells. Int J Mol Sci. 2020;21(10).

  73. Liu Y, Ren H Z, Zhou Y, et al. The hypoxia conditioned mesenchymal stem cells promote hepatocellular carcinoma progression through YAP mediated lipogenesis reprogramming. J Exp Clin Canc Res. 2019;38.

  74. Shu ZP, Gao Y, Zhang GP, et al. A functional interaction between Hippo-YAP signalling and SREBPs mediates hepatic steatosis in diabetic mice. J Cell Mol Med. 2019;23(5):3616–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Li J, Shao J, Zeng Z, et al. Mechanosensitive turnover of phosphoribosyl pyrophosphate synthetases regulates nucleotide metabolism. Cell Death Different. 2021.

  76. Patra KC, Hay N. The pentose phosphate pathway and cancer. Trends Biochem Sci. 2014;39(8):347–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Santinon G, Brian I, Pocaterra A, et al. dNTP metabolism links mechanical cues and YAP/TAZ to cell growth and oncogene-induced senescence. EMBO J. 2018;37(11).

  78. Xie SA, Zhang T, Wang J, et al. Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1. Biomaterials. 2018;155:203–16.

    Article  CAS  PubMed  Google Scholar 

  79. Mouw JK, Yui Y, Damiano L, et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat Med. 2014;20(4):360–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ghajar CM. A stiffness-mediated oncogenic hammer. Sci Transl Med. 2014;6(237):237fs21.

  81. Guo L, Cui C, Zhang K, et al. Kindlin-2 links mechano-environment to proline synthesis and tumor growth. Nat Commun. 2019;10(1):845.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Yang CS, Stampouloglou E, Kingston NM, et al. Glutamine-utilizing transaminases are a metabolic vulnerability of TAZ/YAP-activated cancer cells. EMBO Rep. 2018;19(6).

  83. Mohamed A, Sun C, De Mello V, et al. The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance is associated with reduced survival in embryonal rhabdomyosarcoma. J Pathol. 2016;240(1):3–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Duan LM, Liu JY, Yu CW, et al. PLCepsilon knockdown prevents serine/glycine metabolism and proliferation of prostate cancer by suppressing YAP. Am J Cancer Res. 2020;10(1):196–210.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Bertero T, Oldham WM, Grasset EM, et al. Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy. Cell Metab. 2019;29(1):124-40.e10.

    Article  CAS  PubMed  Google Scholar 

  86. Cox AG, Hwang KL, Brown KK, et al. Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nat Cell Biol. 2016;18(8):886–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Park YY, Sohn BH, Johnson RL, et al. Yes-associated protein 1 and transcriptional coactivator with PDZ-binding motif activate the mammalian target of rapamycin complex 1 pathway by regulating amino acid transporters in hepatocellular carcinoma. Hepatology. 2016;63(1):159–72.

    Article  CAS  PubMed  Google Scholar 

  88. Hansen CG, Ng YL, Lam WL, et al. The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1. Cell Res. 2015;25(12):1299–313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Edwards DN, Ngwa VM, Wang S, et al. The receptor tyrosine kinase EphA2 promotes glutamine metabolism in tumors by activating the transcriptional coactivators YAP and TAZ. Sci Signal. 2017;10(508).

  90. Walma DAC, Yamada KM. The extracellular matrix in development. Development. 2020;147(10).

  91. Leiva O, Leon C, Kah Ng S, et al. The role of extracellular matrix stiffness in megakaryocyte and platelet development and function. Am J Hematol. 2018;93(3):430–41.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Abbonante V, Di Buduo CA, Gruppi C, et al. A new path to platelet production through matrix sensing. Haematologica. 2017;102(7):1150–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Smith LR, Cho S, Discher DE. Stem Cell Differentiation is Regulated by Extracellular Matrix Mechanics. Physiology. 2018;33(1):16–25.

    Article  PubMed  Google Scholar 

  94. Evers TMJ, Holt LJ, Alberti S, et al. Reciprocal regulation of cellular mechanics and metabolism. Nat Metab. 2021;3(4):456–68.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Cai Z, Gong Z, Li Z, et al. Vascular Extracellular Matrix Remodeling and Hypertension. Antioxid Redox Signal. 2021;34(10):765–83.

    Article  CAS  PubMed  Google Scholar 

  96. Koliaraki V, Prados A, Armaka M, et al. The mesenchymal context in inflammation, immunity and cancer. Nat Immunol. 2020;21(9):974–82.

    Article  CAS  PubMed  Google Scholar 

  97. Frangogiannis NG. The Extracellular Matrix in Ischemic and Nonischemic Heart Failure. Circ Res. 2019;125(1):117–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Torrino S, Grasset EM, Audebert S, et al. Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis. Cell Metab. 2021;33(7):1342-57.e10.

    Article  CAS  PubMed  Google Scholar 

  99. Selman M, Pardo A. Fibroageing: An ageing pathological feature driven by dysregulated extracellular matrix-cell mechanobiology. Ageing Res Rev. 2021;70: 101393.

    Article  CAS  PubMed  Google Scholar 

  100. Huang S, Ingber DE. Cell tension, matrix mechanics, and cancer development. Cancer Cell. 2005;8(3):175–6.

    Article  CAS  PubMed  Google Scholar 

  101. Mohammadi H, Sahai E. Mechanisms and impact of altered tumour mechanics. Nat Cell Biol. 2018;20(7):766–74.

    Article  CAS  PubMed  Google Scholar 

  102. Jang M, An J, Oh SW, et al. Matrix stiffness epigenetically regulates the oncogenic activation of the Yes-associated protein in gastric cancer. Nature Biomedical Engineering. 2021;5(1):114–23.

    Article  CAS  PubMed  Google Scholar 

  103. Patwardhan S, Mahadik P, Shetty O, et al. ECM stiffness-tuned exosomes drive breast cancer motility through thrombospondin-1. Biomaterials. 2021;279:121185.

    Article  CAS  PubMed  Google Scholar 

  104. Lampi MC, Reinhart-King CA. Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials. Sci Transl Med. 2018;10(422).

  105. Gkretsi V, Stylianopoulos T. Cell Adhesion and Matrix Stiffness: Coordinating Cancer Cell Invasion and Metastasis. Front Oncol. 2018;8(145).

  106. Zhang W, Zhang S, Zhang W, et al. Matrix stiffness and its influence on pancreatic diseases. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2021;1876(1):188583.

  107. Rockey DC, Bell PD, Hill JA. Fibrosis–a common pathway to organ injury and failure. N Engl J Med. 2015;372(12):1138–49.

    Article  CAS  PubMed  Google Scholar 

  108. Noguchi S, Saito A, Mikami Y, et al. TAZ contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts. Sci Rep. 2017;7:42595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Noguchi S, Saito A, Nagase T. YAP/TAZ Signaling as a Molecular Link between Fibrosis and Cancer. Int J Mol Sci. 2018;19(11):3674.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Henderson NC, Rieder F, Wynn TA. Fibrosis: From mechanisms to medicines. Nature. 2020;587(7835):555–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Tao He and Qingfeng Tang for editing and revising the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China grants 81872218 (R.L.).

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  1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, 14, Section 3, Renminnan Road, Chengdu, 610041, Sichuan, China

    Xiaoyu Liao, Xin Li & Rui Liu

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Liao, X., Li, X. & Liu, R. Extracellular-matrix mechanics regulate cellular metabolism: A ninja warrior behind mechano-chemo signaling crosstalk. Rev Endocr Metab Disord 24, 207–220 (2023). https://doi.org/10.1007/s11154-022-09768-z

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