Abstract
Purpose
The technology of reprogramming a terminally differentiated cell to an embryonic-like state uncovered the possibility of reprogramming a malignant cell back to a more manageable stem cell-like state. Since the current cancer models suffer from reflecting heterogeneous tumour structure and limited to express the late-stage markers, the induced pluripotent stem cell (iPSC) technology could provide an alternative model to recapitulate the early stages of cancer. Generation of iPSCs from cancer cells could offer a tool for understanding the mechanisms of tumour initiation–progression in vitro, a platform for studying tumour heterogeneity and origin of cancer stem cells and a source for cancer type-specific drug discovery studies.
Methods
In this review, we discussed the recent findings in reprogramming cancer cells with a special emphasis on similarities between cancer cells and pluripotent cells. We presented the basis of challenges in cancer cell reprogramming including the current problems in reprogramming, cancer-specific epigenetic state and chromosomal aberrations.
Results
Cancer epigenetics represent the major hurdle before the prospective use of cancer iPSCs as a model system and for biomarker research. When the reprogramming process is optimised for cancer cell types, it might serve for two purposes: identification of the specific epigenetic state of cancer as well as reversion of the malignant phenotype to a potentially malignant but manageable state.
Conclusions
Reprogramming cancer cells would serve for our understanding of cancer-specific epigenome and elucidation of overlapping mechanisms shared by cancer-initiating cells and pluripotent cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akhavan-Niaki H, Samadani AA (2014) Molecular insight in gastric cancer induction: an overview of cancer stemness genes. Cell Biochem Biophys 68:463–473. doi:10.1007/s12013-013-9749-7
Bareiss PM et al (2013) SOX2 expression associates with stem cell state in human ovarian carcinoma. Cancer Res 73:5544–5555. doi:10.1158/0008-5472.CAN-12-4177
Bar-Nur O, Russ HA, Efrat S, Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9:17–23. doi:10.1016/j.stem.2011.06.007
Blelloch RH et al (2004) Nuclear cloning of embryonal carcinoma cells. Proc Natl Acad Sci USA 101:13985–13990. doi:10.1073/pnas.0405015101
Boiani M, Scholer HR (2005) Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol 6:872–884. doi:10.1038/nrm1744
Boyer LA et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956. doi:10.1016/j.cell.2005.08.020
Buganim Y, Faddah DA, Jaenisch R (2013) Mechanisms and models of somatic cell reprogramming. Nat Rev Genet 14:427–439. doi:10.1038/nrg3473
Cao L, Bombard J, Cintron K, Sheedy J, Weetall ML, Davis TW (2011) BMI1 as a novel target for drug discovery in cancer. J Cell Biochem 112:2729–2741. doi:10.1002/jcb.23234
Carette JE et al (2010) Generation of iPSCs from cultured human malignant cells. Blood 115:4039–4042. doi:10.1182/blood-2009-07-231845
Chen X et al (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133:1106–1117. doi:10.1016/j.cell.2008.04.043
Chiou SH et al (2008) Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res 14:4085–4095. doi:10.1158/1078-0432.CCR-07-4404
Corominas-Faja B et al (2013) Nuclear reprogramming of luminal-like breast cancer cells generates Sox2-overexpressing cancer stem-like cellular states harboring transcriptional activation of the mTOR pathway. Cell Cycle 12:3109–3124. doi:10.4161/cc.26173
Dang CV (2007) The interplay between MYC and HIF in the Warburg effect. Ernst Schering Found Symp Proc 4:35–53
Dawson MA, Kouzarides T (2012) Cancer epigenetics: from mechanism to therapy. Cell 150:12–27. doi:10.1016/j.cell.2012.06.013
Ding X, Wang X, Sontag S, Qin J, Wanek P, Lin Q, Zenke M (2014) The polycomb protein Ezh2 impacts on induced pluripotent stem cell generation. Stem Cells Dev 23:931–940. doi:10.1089/scd.2013.0267
Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463. doi:10.1038/nature02625
Eminli S, Utikal J, Arnold K, Jaenisch R, Hochedlinger K (2008) Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expression. Stem Cells 26:2467–2474. doi:10.1634/stemcells.2008-0317
Eminli S et al (2009) Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 41:968–976. doi:10.1038/ng.428
Folmes CD, Terzic A (2016) Energy metabolism in the acquisition and maintenance of stemness. Semi Cell Dev Biol. doi:10.1016/j.semcdb.2016.02.010
Folmes CD et al (2011) Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab 14:264–271. doi:10.1016/j.cmet.2011.06.011
Folmes CD, Martinez-Fernandez A, Faustino RS, Yamada S, Perez-Terzic C, Nelson TJ, Terzic A (2013) Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells. J Cardiovasc Transl Res 6:10–21. doi:10.1007/s12265-012-9431-2
Gandre-Babbe S et al (2013) Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia. Blood 121:4925–4929. doi:10.1182/blood-2013-01-478412
Gangemi RM et al (2009) SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells 27:40–48. doi:10.1634/stemcells.2008-0493
Giorgetti A et al (2009) Generation of induced pluripotent stem cells from human cord blood using OCT4 and SOX2. Cell Stem Cell 5:353–357. doi:10.1016/j.stem.2009.09.008
Giorgetti A, Montserrat N, Rodriguez-Piza I, Azqueta C, Veiga A, Izpisua Belmonte JC (2010) Generation of induced pluripotent stem cells from human cord blood cells with only two factors: Oct4 and Sox2. Nat Protoc 5:811–820. doi:10.1038/nprot.2010.16
Gurdon JB (1962) The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10:622–640
Hawkins RD et al (2010) Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6:479–491. doi:10.1016/j.stem.2010.03.018
Heng HH, Bremer SW, Stevens JB, Ye KJ, Liu G, Ye CJ (2009) Genetic and epigenetic heterogeneity in cancer: a genome-centric perspective. J Cell Physiol 220:538–547. doi:10.1002/jcp.21799
Herreros-Villanueva M et al (2013) SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells. Oncogenesis 2:e61. doi:10.1038/oncsis.2013.23
Hochedlinger K, Plath K (2009) Epigenetic reprogramming and induced pluripotency. Development 136:509–523. doi:10.1242/dev.020867
Hochedlinger K, Blelloch R, Brennan C, Yamada Y, Kim M, Chin L, Jaenisch R (2004) Reprogramming of a melanoma genome by nuclear transplantation. Genes Dev 18:1875–1885. doi:10.1101/gad.1213504
Hou P et al (2013) Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341:651–654. doi:10.1126/science.1239278
Hu K et al (2011) Efficient generation of transgene-free induced pluripotent stem cells from normal and neoplastic bone marrow and cord blood mononuclear cells. Blood 117:e109–e119. doi:10.1182/blood-2010-07-298331
Huangfu D et al (2008) Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26:1269–1275. doi:10.1038/nbt.1502
Hussein SM et al (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471:58–62. doi:10.1038/nature09871
Hutz K et al (2014) The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells. Carcinogenesis 35:942–950. doi:10.1093/carcin/bgt410
Ichida JK et al (2014) Notch inhibition allows oncogene-independent generation of iPS cells. Nat Chem Biol 10:632–639. doi:10.1038/nchembio.1552
Iskender B, Izgi K, Canatan H (2016) Reprogramming bladder cancer cells for studying cancer initiation and progression. Tumour Biol. doi:10.1007/s13277-016-5226-4
Islam SM et al (2015) Sendai virus-mediated expression of reprogramming factors promotes plasticity of human neuroblastoma cells. Cancer Sci 106:1351–1361. doi:10.1111/cas.12746
Iv Santaliz-Ruiz LE, Xie X, Old M, Teknos TN, Pan Q (2014) Emerging role of nanog in tumorigenesis and cancer stem cells. Int J Cancer 135:2741–2748. doi:10.1002/ijc.28690
Ivanov NA et al (2016) Strong components of epigenetic memory in cultured human fibroblasts related to site of origin and donor age. PLoS Genet 12:e1005819. doi:10.1371/journal.pgen.1005819
Jeter CR, Yang T, Wang J, Chao HP, Tang DG (2015) Concise review: NANOG in cancer stem cells and tumor development: an update and outstanding questions. Stem Cells 33:2381–2390. doi:10.1002/stem.2007
Kamachi Y, Uchikawa M, Kondoh H (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 16:182–187
Kang PJ et al (2014) Reprogramming of mouse somatic cells into pluripotent stem-like cells using a combination of small molecules. Biomaterials 35:7336–7345. doi:10.1016/j.biomaterials.2014.05.015
Kelly TK, De Carvalho DD, Jones PA (2010) Epigenetic modifications as therapeutic targets. Nat Biotechnol 28:1069–1078. doi:10.1038/nbt.1678
Kim JB et al (2009) Induced pluripotency in adult neural stem cells. Cell 136:411–419. doi:10.1016/j.cell.2009.01.023
Kim K et al (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467:285–290. doi:10.1038/nature09342
Kim J et al (2013) An iPSC line from human pancreatic ductal adenocarcinoma undergoes early to invasive stages of pancreatic cancer progression. Cell Rep 3:2088–2099. doi:10.1016/j.celrep.2013.05.036
Kimura T et al (2015) Pluripotent stem cells derived from mouse primordial germ cells by small molecule compounds. Stem Cells 33:45–55. doi:10.1002/stem.1838
Koche RP et al (2011) Reprogramming factor expression initiates widespread targeted chromatin remodeling. Cell Stem Cell 8:96–105. doi:10.1016/j.stem.2010.12.001
Kong D, Banerjee S, Ahmad A, Li Y, Wang Z, Sethi S, Sarkar FH (2010) Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS ONE 5:e12445. doi:10.1371/journal.pone.0012445
Kotini AG et al (2015) Functional analysis of a chromosomal deletion associated with myelodysplastic syndromes using isogenic human induced pluripotent stem cells. Nat Biotechnol 33:646–655. doi:10.1038/nbt.3178
Kumano K et al (2012) Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood 119:6234–6242. doi:10.1182/blood-2011-07-367441
Ladewig J, Koch P, Brustle O (2013) Leveling Waddington: the emergence of direct programming and the loss of cell fate hierarchies. Nat Rev Mol Cell Biol 14:225–236
Lee HJ et al (2015a) Positive expression of NANOG, mutant p53, and CD44 is directly associated with clinicopathological features and poor prognosis of oral squamous cell carcinoma. BMC Oral Health 15:153. doi:10.1186/s12903-015-0120-9
Lee SR et al (2015b) Activation of EZH2 and SUZ12 regulated by E2F1 predicts the disease progression and aggressive characteristics of bladder cancer. Clin Cancer Res 21:5391–5403. doi:10.1158/1078-0432.CCR-14-2680
Lin T, Wu S (2015) Reprogramming with small molecules instead of exogenous transcription factors. Stem Cells Int 2015:794632. doi:10.1155/2015/794632
Lin SL, Chang DC, Chang-Lin S, Lin CH, Wu DT, Chen DT, Ying SY (2008) Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA 14:2115–2124. doi:10.1261/rna.1162708
Lin T, Ding YQ, Li JM (2012a) Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol 29:878–885. doi:10.1007/s12032-011-9860-9
Lin ZS, Chu HC, Yen YC, Lewis BC, Chen YW (2012b) Kruppel-like factor 4, a tumor suppressor in hepatocellular carcinoma cells reverts epithelial mesenchymal transition by suppressing slug expression. PLoS ONE 7:e43593. doi:10.1371/journal.pone.0043593
Lister R et al (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471:68–73. doi:10.1038/nature09798
Liu XF, Yang WT, Xu R, Liu JT, Zheng PS (2014a) Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells. PLoS ONE 9:e87092. doi:10.1371/journal.pone.0087092
Liu Y et al (2014b) Reprogramming of MLL-AF9 leukemia cells into pluripotent stem cells. Leukemia 28:1071–1080. doi:10.1038/leu.2013.304
Loh YH et al (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–440. doi:10.1038/ng1760
Mahalingam D, Kong CM, Lai J, Tay LL, Yang H, Wang X (2012) Reversal of aberrant cancer methylome and transcriptome upon direct reprogramming of lung cancer cells. Sci Rep 2:592. doi:10.1038/srep00592
Masui S et al (2007) Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol 9:625–635. doi:10.1038/ncb1589
Mathieu J et al (2011) HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 71:4640–4652. doi:10.1158/0008-5472.CAN-10-3320
Mayshar Y et al (2010) Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7:521–531. doi:10.1016/j.stem.2010.07.017
Meacham CE, Morrison SJ (2013) Tumour heterogeneity and cancer cell plasticity. Nature 501:328–337. doi:10.1038/nature12624
Meng HM et al (2010) Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther 9:295–302. doi:10.4161/cbt.9.4.10666
Miller DM, Thomas SD, Islam A, Muench D, Sedoris K (2012) c-Myc and cancer metabolism. Clin Cancer Res 18:5546–5553. doi:10.1158/1078-0432.CCR-12-0977
Mimeault M, Batra SK (2011) Frequent gene products and molecular pathways altered in prostate cancer- and metastasis-initiating cells and their progenies and novel promising multitargeted therapies. Mol Med 17:949–964. doi:10.2119/molmed.2011.00115
Mishra A, Brat DJ, Verma M (2015) P53 tumor suppression network in cancer epigenetics. Methods Mol Biol 1238:597–605. doi:10.1007/978-1-4939-1804-1_31
Miyoshi N et al (2010) Defined factors induce reprogramming of gastrointestinal cancer cells. Proc Nat Acad Sci USA 107:40–45. doi:10.1073/pnas.0912407107
Mohyeldin A, Garzon-Muvdi T, Quinones-Hinojosa A (2010) Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell 7:150–161. doi:10.1016/j.stem.2010.07.007
Moon JH et al (2011) Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1. Cell Res 21:1305–1315. doi:10.1038/cr.2011.107
Moon JH et al (2013) Reprogramming of mouse fibroblasts into induced pluripotent stem cells with Nanog. Biochem Biophys Res Commun 431:444–449. doi:10.1016/j.bbrc.2012.12.149
Moore JBt et al (2015) Epigenetic reprogramming and re-differentiation of a Ewing sarcoma cell line. Front Cell Dev Biol 3:15. doi:10.3389/fcell.2015.00015
Munoz P, Iliou MS, Esteller M (2012) Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol 6:620–636. doi:10.1016/j.molonc.2012.10.006
Nakagawa M et al (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106. doi:10.1038/nbt1374
Nandan MO, Yang VW (2009) The role of Kruppel-like factors in the reprogramming of somatic cells to induced pluripotent stem cells. Histol Histopathol 24:1343–1355
Nie Z et al (2012) c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic. Stem cells Cell 151:68–79. doi:10.1016/j.cell.2012.08.033
Niibe K et al (2011) Purified mesenchymal stem cells are an efficient source for iPS cell induction. PLoS ONE 6:e17610. doi:10.1371/journal.pone.0017610
Noguchi K et al (2015) Susceptibility of pancreatic cancer stem cells to reprogramming. Cancer Sci 106:1182–1187. doi:10.1111/cas.12734
Ohi Y et al (2011) Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol 13:541–549. doi:10.1038/ncb2239
Ohnishi K et al (2014) Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell 156:663–677. doi:10.1016/j.cell.2014.01.005
Oshima N et al (2014) Induction of cancer stem cell properties in colon cancer cells by defined factors. PLoS ONE 9:e101735. doi:10.1371/journal.pone.0101735
Panopoulos AD et al (2012) The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res 22:168–177. doi:10.1038/cr.2011.177
Papp B, Plath K (2011) Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape. Cell Res 21:486–501. doi:10.1038/cr.2011.28
Phetfong J, Supokawej A, Wattanapanitch M, Kheolamai P, Yaowalak U, Issaragrisil S (2016) Cell type of origin influences iPSC generation and differentiation to cells of the hematoendothelial lineage. Cell Tissue Res 365:101–112. doi:10.1007/s00441-016-2369-y
Pirozzi G et al (2011) Epithelial to mesenchymal transition by TGFbeta-1 induction increases stemness characteristics in primary non small cell lung cancer cell line. PLoS ONE 6:e21548. doi:10.1371/journal.pone.0021548
Polo JM et al (2010) Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28:848–855. doi:10.1038/nbt.1667
Postovit LM et al (2008) Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype of aggressive cancer cells. Proc Nat Acad Sci USA 105:4329–4334. doi:10.1073/pnas.0800467105
Rais Y et al (2013) Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502:65–70. doi:10.1038/nature12587
Rasmussen MA et al (2014) Transient p53 suppression increases reprogramming of human fibroblasts without affecting apoptosis and DNA damage. Stem Cell Rep 3:404–413. doi:10.1016/j.stemcr.2014.07.006
Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P (2005) Transcriptional regulation of nanog by OCT4 and SOX2. J Biol Chem 280:24731–24737. doi:10.1074/jbc.M502573200
Ron-Bigger S, Bar-Nur O, Isaac S, Bocker M, Lyko F, Eden A (2010) Aberrant epigenetic silencing of tumor suppressor genes is reversed by direct reprogramming. Stem Cells 28:1349–1354. doi:10.1002/stem.468
Rouhani F, Kumasaka N, de Brito MC, Bradley A, Vallier L, Gaffney D (2014) Genetic background drives transcriptional variation in human induced pluripotent stem cells. PLoS Genet 10:e1004432. doi:10.1371/journal.pgen.1004432
Ruiz S et al (2012) Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells. Pro Nat Acad Sci USA 109:16196–16201. doi:10.1073/pnas.1202352109
Rybak AP, Tang D (2013) SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells. Cell Signal 25:2734–2742. doi:10.1016/j.cellsig.2013.08.041
Sanchez-Freire V et al (2014) Effect of human donor cell source on differentiation and function of cardiac induced pluripotent stem cells. J Am Coll Cardiol 64:436–448. doi:10.1016/j.jacc.2014.04.056
Semi K, Yamada Y (2015) Induced pluripotent stem cell technology for dissecting the cancer epigenome. Cancer Sci 106:1251–1256. doi:10.1111/cas.12758
Seymour T, Twigger AJ, Kakulas F (2015) Pluripotency genes and their functions in the normal and aberrant breast and brain. Int J Mol Sci 16:27288–27301. doi:10.3390/ijms161126024
Shan J et al (2012) Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma. Hepatology 56:1004–1014. doi:10.1002/hep.25745
Singh S, Trevino J, Bora-Singhal N, Coppola D, Haura E, Altiok S, Chellappan SP (2012) EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer. Mol Cancer 11:73. doi:10.1186/1476-4598-11-73
Singh VK, Kalsan M, Kumar N, Saini A, Chandra R (2015) Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol 3:2. doi:10.3389/fcell.2015.00002
Stadtfeld M, Hochedlinger K (2010) Induced pluripotency: history, mechanisms, and applications. Genes Dev 24:2239–2263. doi:10.1101/gad.1963910
Stricker SH et al (2013) Widespread resetting of DNA methylation in glioblastoma-initiating cells suppresses malignant cellular behavior in a lineage-dependent manner. Genes Dev 27:654–669. doi:10.1101/gad.212662.112
Tafani M et al (2014) Reprogramming cancer cells in endocrine-related tumors: open issues. Curr Med Chem 21:1146–1151
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. doi:10.1016/j.cell.2006.07.024
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. doi:10.1016/j.cell.2007.11.019
Timp W, Feinberg AP (2013) Cancer as a dysregulated epigenome allowing cellular growth advantage at the expense of the host. Nat Rev Cancer 13:497–510. doi:10.1038/nrc3486
Tobin SC, Kim K (2012) Generating pluripotent stem cells: differential epigenetic changes during cellular reprogramming. FEBS Lett 586:2874–2881. doi:10.1016/j.febslet.2012.07.024
Tonini T, D’Andrilli G, Fucito A, Gaspa L, Bagella L (2008) Importance of Ezh2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements. J Cell Physiol 214:295–300. doi:10.1002/jcp.21241
Utikal J, Maherali N, Kulalert W, Hochedlinger K (2009) Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J Cell Sci 122:3502–3510. doi:10.1242/jcs.054783
Vaira V et al (2013) Regulation of lung cancer metastasis by Klf4-Numb-like signaling. Cancer Res 73:2695–2705. doi:10.1158/0008-5472.CAN-12-4232
Vencio EF et al (2012) Reprogramming of prostate cancer-associated stromal cells to embryonic stem-like. Prostate 72:1453–1463. doi:10.1002/pros.22497
Vidal SE, Amlani B, Chen T, Tsirigos A, Stadtfeld M (2014) Combinatorial modulation of signaling pathways reveals cell-type-specific requirements for highly efficient and synchronous iPSC reprogramming. Stem Cell Rep 3:574–584. doi:10.1016/j.stemcr.2014.08.003
Villasante A, Piazzolla D, Li H, Gomez-Lopez G, Djabali M, Serrano M (2011) Epigenetic regulation of Nanog expression by Ezh2 in pluripotent stem cells. Cell Cycle 10:1488–1498
Virani S, Colacino JA, Kim JH, Rozek LS (2012) Cancer epigenetics: a brief review. ILAR J 53:359–369. doi:10.1093/ilar.53.3-4.359
Wang J et al (2013) Generation of induced pluripotent stem cells with high efficiency from human umbilical cord blood mononuclear cells. Genomics Proteomics Bioinformatics 11:304–311. doi:10.1016/j.gpb.2013.08.002
Wang D et al (2014) Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients. Oncotarget 5:10803–10815. doi:10.18632/oncotarget.2506
Weina K, Utikal J (2014) SOX2 and cancer: current research and its implications in the clinic. Clin Transl Med 3:19. doi:10.1186/2001-1326-3-19
Weinhold B (2006) Epigenetics: the science of change. Environ Health Perspect 114:A160–A167
Wernig M, Meissner A, Cassady JP, Jaenisch R (2008) c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2:10–12. doi:10.1016/j.stem.2007.12.001
Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810–813. doi:10.1038/385810a0
Wong CW et al (2010) Kruppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells. Stem Cells 28:1510–1517. doi:10.1002/stem.477
Xie B, Zhang H, Wei R, Li Q, Weng X, Kong Q, Liu Z (2016) Histone H3 lysine 27 trimethylation acts as an epigenetic barrier in porcine nuclear reprogramming. Reproduction 151:9–16. doi:10.1530/REP-15-0338
Yi L, Lu C, Hu W, Sun Y, Levine AJ (2012) Multiple roles of p53-related pathways in somatic cell reprogramming and stem cell differentiation. Cancer Res 72:5635–5645. doi:10.1158/0008-5472.CAN-12-1451
Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S (2009) Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5:237–241. doi:10.1016/j.stem.2009.08.001
Yu J et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920. doi:10.1126/science.1151526
Yu F et al (2011) Kruppel-like factor 4 (KLF4) is required for maintenance of breast cancer stem cells and for cell migration and invasion. Oncogene 30:2161–2172. doi:10.1038/onc.2010.591
Yulin X, Lizhen L, Lifei Z, Shan F, Ru L, Kaimin H, Huang H (2012) Efficient generation of induced pluripotent stem cells from human bone marrow mesenchymal stem cells. Folia Biol 58:221–230
Zammarchi F et al (2011) KLF4 is a novel candidate tumor suppressor gene in pancreatic ductal carcinoma. Am J Pathol 178:361–372. doi:10.1016/j.ajpath.2010.11.021
Zhang X, Cruz FD, Terry M, Remotti F, Matushansky I (2013) Terminal differentiation and loss of tumorigenicity of human cancers via pluripotency-based reprogramming. Oncogene 32:2249–2260. doi:10.1038/onc.2012.237
Zhu S et al (2010) Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7:651–655. doi:10.1016/j.stem.2010.11.015
Zilfou JT, Lowe SW (2009) Tumor suppressive functions of p53. Cold Spring Harb Perspect Biol 1:a001883. doi:10.1101/cshperspect.a001883
Acknowledgments
This study was supported by the grant from The Scientific and Technological Research Council of Turkey (No: 114S452 and 113S927).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Rights and permissions
About this article
Cite this article
Izgi, K., Canatan, H. & Iskender, B. Current status in cancer cell reprogramming and its clinical implications. J Cancer Res Clin Oncol 143, 371–383 (2017). https://doi.org/10.1007/s00432-016-2258-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-016-2258-5