Pluripotent transcription factors possess distinct roles in normal versus transformed human stem cells

• Published in: PloS one Vol. 4; no. 11; p. e8065
• Main Authors: Ji, Junfeng, Werbowetski-Ogilvie, Tamra E, Zhong, Bonan, Hong, Seok-Ho, Bhatia, Mickie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.11.2009; Public Library of Science (PLoS)
• Subjects: Apoptosis; Bifurcations; Cancer; Cancer research; Cell Biology/Developmental Molecular Mechanisms; Cell Differentiation; Cell Line; Cell Line, Transformed; Cell self-renewal; Cell survival; Developmental Biology/Stem Cells; DNA binding proteins; Embryos; Flow Cytometry - methods; Gene expression; Glycoproteins; Green Fluorescent Proteins - metabolism; Homeodomain Proteins - metabolism; Humans; Hypersensitivity; Jargon; Lentivirus - metabolism; Medical research; Models, Biological; Nanog Homeobox Protein; Neoplastic Stem Cells - cytology; Oct-4 protein; Octamer Transcription Factor-3 - metabolism; Oncology; Pluripotency; Pluripotent Stem Cells - cytology; Rodents; Stem cells; Survival; Teratoma - metabolism; Transcription factors; Transcription Factors - metabolism; Transgenic animals; Tumors; Ontario Canada; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008065

Cancer and normal stem cells (SCs) share proliferative properties of self-renewal and expression of key transcription factors (TFs). Despite similar TF identities, the functional role of specific TFs responsible for retaining SC state has yet to be examined in cancer. Here, we compare the role of Oct4 and Nanog, two-core pluripotent TFs, in transformed (t-hPSCs), and normal human pluripotent stem cells (hPSCs). Unlike normal SCs, self-renewal and survival of t-hPSCs were found to be independent of Oct4. In contrast, t-hPSCs exhibit hypersensitivity to reduction in Nanog and demonstrate complete loss of self-renewal coupled with apoptosis. Dual and sequential knockdown of Oct4 and Nanog revealed that sensitivity of t-hPSCs to Nanog was Oct4 dependent. Our study indicates a bifurcation for the role of two-core SC and cancer related TFs in self-renewal and survival processes. We suggest that the divergent roles of these TFs establish a paradigm to develop novel therapeutics towards selective destruction of aggressive tumors harboring cancer stem cells (CSCs) with similar molecular signatures.