title: The emerging roles of Oct4 in tumor-initiating cells.
abstract: Octamer-binding transcription factor 4 (Oct4), a homeodomain transcription factor, is well established as a master factor controlling the self-renewal and pluripotency of pluripotent stem cells. Also, a large body of research has documented the detection of Oct4 in tumor cells and tissues and has indicated its enrichment in a subpopulation of undifferentiated tumor-initiating cells (TICs) that critically account for tumor initiation, metastasis, and resistance to anticancer therapies. There is circumstantial evidence for low-level expression of Oct4 in cancer cells and TICs, and the participation of Oct4 in various TIC functions such as its self-renewal and survival, epithelial-mesenchymal transition (EMT) and metastasis, and drug resistance development is implicated from considerable Oct4 knockdown and overexpression-based studies. In a few studies, efforts have been made to identify Oct4 target genes in TICs of different sources. Based on such information, Oct4 in TICs appears to act via mechanisms quite distinct from those in pluripotent stem cells, and a main challenge for future studies is to unravel the molecular mechanisms of action of Oct4, particularly to address the question on how such low levels of Oct4 may exert its functions in TICs. Acquiring cells from their native microenvironment that are of high enough quantity and purity is the key to reliably analyze Oct4 functions and its target genes in TICs, and the information gained may greatly facilitate targeting and eradicating those cells.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; and Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania yingjiewang@zju.edu.cn.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania.
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000502:physiology
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human
keywords: Oct4; drug resistance; epithelial-mesenchymal transition; self-renewal; tumor-initiating cells