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

Bibliographic Details
Title: Pluripotent transcription factors possess distinct roles in normal versus transformed human stem cells.
Authors: Junfeng Ji, Tamra E Werbowetski-Ogilvie, Bonan Zhong, Seok-Ho Hong, Mickie Bhatia
Source: PLoS ONE, Vol 4, Iss 11, p e8065 (2009)
Publisher Information: Public Library of Science (PLoS), 2009.
Publication Year: 2009
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: http://europepmc.org/articles/PMC2778551?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0008065
Access URL: https://doaj.org/article/42c0f1fd35bd4a2d955f027363378259
Accession Number: edsdoj.42c0f1fd35bd4a2d955f027363378259
Database: Directory of Open Access Journals
More Details
ISSN:19326203
DOI:10.1371/journal.pone.0008065
Published in:PLoS ONE
Language:English