Reprogramming of Cancer Cells into Induced Pluripotent Stem Cells Questioned.

Cancer cell reprogramming Induced pluripotent stem cells Pluripotency RNA-sequencing analysis iPSC generation

Journal

International journal of stem cells
ISSN: 2005-3606
Titre abrégé: Int J Stem Cells
Pays: Korea (South)
ID NLM: 101497587

Informations de publication

Date de publication:
30 Nov 2019
Historique:
received: 17 05 2019
revised: 26 07 2019
accepted: 27 07 2019
pubmed: 2 9 2019
medline: 2 9 2019
entrez: 2 9 2019
Statut: ppublish

Résumé

Several recent studies have claimed that cancer cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, in most cases, cancer cells seem to be resistant to cellular reprogramming. Furthermore, the underlying mechanisms of limited reprogramming in cancer cells are largely unknown. Here, we identified the candidate barrier genes and their target genes at the early stage of reprogramming for investigating cancer reprogramming. We tried induction of pluripotency in normal human fibroblasts (BJ) and both human benign (MCF10A) and malignant (MCF7) breast cancer cell lines using a classical retroviral reprogramming method. We conducted RNA-sequencing analysis to compare the transcriptome of the three cell lines at early stage of reprogramming. We could generate iPSCs from BJ, whereas we were unable to obtain iPSCs from cancer cell lines. To address the underlying mechanism of limited reprogramming in cancer cells, we identified 29 the candidate barrier genes based on RNA-sequencing data. In addition, we found 40 their target genes using Cytoscape software. Our data suggest that these genes might one of the roadblock for cancer cell reprogramming. Furthermore, we provide new insights into application of iPSCs technology in cancer cell field for therapeutic purposes.

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
Several recent studies have claimed that cancer cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, in most cases, cancer cells seem to be resistant to cellular reprogramming. Furthermore, the underlying mechanisms of limited reprogramming in cancer cells are largely unknown. Here, we identified the candidate barrier genes and their target genes at the early stage of reprogramming for investigating cancer reprogramming.
METHODS METHODS
We tried induction of pluripotency in normal human fibroblasts (BJ) and both human benign (MCF10A) and malignant (MCF7) breast cancer cell lines using a classical retroviral reprogramming method. We conducted RNA-sequencing analysis to compare the transcriptome of the three cell lines at early stage of reprogramming.
RESULTS RESULTS
We could generate iPSCs from BJ, whereas we were unable to obtain iPSCs from cancer cell lines. To address the underlying mechanism of limited reprogramming in cancer cells, we identified 29 the candidate barrier genes based on RNA-sequencing data. In addition, we found 40 their target genes using Cytoscape software.
CONCLUSIONS CONCLUSIONS
Our data suggest that these genes might one of the roadblock for cancer cell reprogramming. Furthermore, we provide new insights into application of iPSCs technology in cancer cell field for therapeutic purposes.

Identifiants

pubmed: 31474029
pii: ijsc19067
doi: 10.15283/ijsc19067
pmc: PMC6881048
doi:

Types de publication

Journal Article

Langues

eng

Pagination

430-439

Références

Cell Rep. 2017 Dec 19;21(12):3390-3397
pubmed: 29262320
Cell Reprogram. 2015 Feb;17(1):7-18
pubmed: 25549177
Cancer Sci. 2015 Sep;106(9):1182-7
pubmed: 26298849
Breast Cancer Res Treat. 1987;9(2):111-21
pubmed: 3620713
J Cancer Res Clin Oncol. 2017 Mar;143(3):371-383
pubmed: 27620745
Stem Cell Reports. 2017 May 9;8(5):1379-1391
pubmed: 28392221
Cell Rep. 2013 Jun 27;3(6):2088-99
pubmed: 23791528
Nat Biotechnol. 2013 Jan;31(1):46-53
pubmed: 23222703
Nat Biotechnol. 2010 May;28(5):511-5
pubmed: 20436464
PLoS One. 2015 Jul 06;10(7):e0131285
pubmed: 26147507
Cell. 2005 Sep 23;122(6):947-56
pubmed: 16153702
Nat Rev Cancer. 2004 Feb;4(2):143-53
pubmed: 14732866
Cell Stem Cell. 2015 Jun 4;16(6):591-600
pubmed: 26046759
BMC Bioinformatics. 2014 Jun 12;15:182
pubmed: 24925680
BMC Genomics. 2018 Jan 3;19(1):9
pubmed: 29298685
J Neurooncol. 2019 Jan;141(2):289-301
pubmed: 30460631
J Cancer. 2017 Sep 12;8(16):3131-3141
pubmed: 29158785
Cell Cycle. 2013 Sep 15;12(18):3109-24
pubmed: 23974095
Nat Biotechnol. 2008 Nov;26(11):1276-84
pubmed: 18931654
Mol Cancer Ther. 2009 Dec;8(12):3191-202
pubmed: 19934278
Cancer Res. 2011 Jul 1;71(13):4640-52
pubmed: 21712410
RNA. 2008 Oct;14(10):2115-24
pubmed: 18755840
J Cell Sci. 2009 Oct 1;122(Pt 19):3502-10
pubmed: 19723802
Anticancer Res. 2017 Jul;37(7):3367-3377
pubmed: 28668824
Oncogene. 2014 Jan 30;33(5):643-52
pubmed: 23318426
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell. 2007 Nov 30;131(5):861-72
pubmed: 18035408
Cell. 2015 Jul 16;162(2):412-424
pubmed: 26186193
PLoS Biol. 2010 Jul 13;8(7):e1000423
pubmed: 20644641
Nat Methods. 2012 Nov;9(11):1069-76
pubmed: 23132118
Oncogene. 2013 May 2;32(18):2249-60, 2260.e1-21
pubmed: 22777357
Tumour Biol. 2016 Oct;37(10):13237-13245
pubmed: 27456363
Oncotarget. 2016 Oct 25;7(43):69536-69548
pubmed: 27588501
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):40-5
pubmed: 20018687
Int J Cancer. 2013 Mar 15;132(6):1240-8
pubmed: 23180619
Science. 2007 Dec 21;318(5858):1917-20
pubmed: 18029452
Cell Stem Cell. 2010 Jul 2;7(1):15-9
pubmed: 20621044

Auteurs

Jin Seok Bang (JS)

Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea.
Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.

Na Young Choi (NY)

Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea.
Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.

Minseong Lee (M)

Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea.
Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.

Kisung Ko (K)

Department of Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.

Yo Seph Park (YS)

Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea.
Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.

Kinarm Ko (K)

Department of Stem Cell Biology, Konkuk University School of Medicine, Seoul, Korea.
Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul, Korea.
Research Institute of Medical Science, Konkuk University, Seoul, Korea.

Classifications MeSH