Top

Journal of Cancer Research and Clinical Oncology

Published in:

01-03-2017 | Review – Cancer Research

Current status in cancer cell reprogramming and its clinical implications

Authors: Kenan Izgi, Halit Canatan, Banu Iskender

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2017

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.

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

Blelloch RH et al (2004) Nuclear cloning of embryonal carcinoma cells. Proc Natl Acad Sci USA 101:13985–13990. doi:10.1073/pnas.0405015101 PubMedPubMedCentral

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

Buganim Y, Faddah DA, Jaenisch R (2013) Mechanisms and models of somatic cell reprogramming. Nat Rev Genet 14:427–439. doi:10.1038/nrg3473 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

Carette JE et al (2010) Generation of iPSCs from cultured human malignant cells. Blood 115:4039–4042. doi:10.1182/blood-2009-07-231845 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

Gurdon JB (1962) The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10:622–640PubMed

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

Hochedlinger K, Plath K (2009) Epigenetic reprogramming and induced pluripotency. Development 136:509–523. doi:10.1242/dev.020867 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

Hussein SM et al (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471:58–62. doi:10.1038/nature09871 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

Kamachi Y, Uchikawa M, Kondoh H (2000) Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 16:182–187PubMedCrossRef

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 PubMedCrossRef

Kelly TK, De Carvalho DD, Jones PA (2010) Epigenetic modifications as therapeutic targets. Nat Biotechnol 28:1069–1078. doi:10.1038/nbt.1678 PubMedPubMedCentralCrossRef

Kim JB et al (2009) Induced pluripotency in adult neural stem cells. Cell 136:411–419. doi:10.1016/j.cell.2009.01.023 PubMedCrossRef

Kim K et al (2010) Epigenetic memory in induced pluripotent stem cells. Nature 467:285–290. doi:10.1038/nature09342 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 14:225–236CrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

Lin T, Wu S (2015) Reprogramming with small molecules instead of exogenous transcription factors. Stem Cells Int 2015:794632. doi:10.1155/2015/794632 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

Lister R et al (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471:68–73. doi:10.1038/nature09798 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

Meacham CE, Morrison SJ (2013) Tumour heterogeneity and cancer cell plasticity. Nature 501:328–337. doi:10.1038/nature12624 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

Nandan MO, Yang VW (2009) The role of Kruppel-like factors in the reprogramming of somatic cells to induced pluripotent stem cells. Histol Histopathol 24:1343–1355PubMedPubMedCentral

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 PubMed

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 PubMedPubMedCentralCrossRef

Noguchi K et al (2015) Susceptibility of pancreatic cancer stem cells to reprogramming. Cancer Sci 106:1182–1187. doi:10.1111/cas.12734 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

Rais Y et al (2013) Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502:65–70. doi:10.1038/nature12587 PubMedCrossRef

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 CrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 CrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

Stadtfeld M, Hochedlinger K (2010) Induced pluripotency: history, mechanisms, and applications. Genes Dev 24:2239–2263. doi:10.1101/gad.1963910 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

Tafani M et al (2014) Reprogramming cancer cells in endocrine-related tumors: open issues. Curr Med Chem 21:1146–1151PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 CrossRef

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 10:1488–1498PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 CrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

Weinhold B (2006) Epigenetics: the science of change. Environ Health Perspect 114:A160–A167PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

Yu J et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920. doi:10.1126/science.1151526 PubMedCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedPubMedCentralCrossRef

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 PubMedCrossRef

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 PubMedCrossRef

Zilfou JT, Lowe SW (2009) Tumor suppressive functions of p53. Cold Spring Harb Perspect Biol 1:a001883. doi:10.1101/cshperspect.a001883 PubMedPubMedCentralCrossRef

Title: Current status in cancer cell reprogramming and its clinical implications
Authors: Kenan Izgi
Halit Canatan
Banu Iskender
Publication date: 01-03-2017
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 3/2017
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-016-2258-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2017

BRAF V600E-dependent role of autophagy in uveal melanoma

Plasma microRNA-103, microRNA-107, and microRNA-194 levels are not biomarkers for human diffuse gastric cancer

Risk factors for intestinal metaplasia in a southeastern Chinese population: an analysis of 28,745 cases

Sentinel lymph node mapping in patients with stage I endometrial carcinoma: a focus on bilateral mapping identification by comparing radiotracer Tc99m with blue dye versus indocyanine green fluorescent dye

53BP1 loss induces chemoresistance of colorectal cancer cells to 5-fluorouracil by inhibiting the ATM–CHK2–P53 pathway

Detection of vertebral metastases: a meta-analysis comparing MRI, CT, PET, BS and BS with SPECT

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage