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


RESULTS
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.


CONCLUSIONS
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.
Ji
Junfeng
J
Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada.
Werbowetski-Ogilvie
Tamra E
TE
Zhong
Bonan
B
Hong
Seok-Ho
SH
Bhatia
Mickie
M
D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D005434:Flow Cytometry / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008954:Models, Biological; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000166:cytology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D013724:Teratoma / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014157:Transcription Factors; D049452:Green Fluorescent Proteins