Transcription factor Oct1 is a somatic and cancer stem cell determinant.

Abstract

Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell function. Oct1(HI) cells in the colon and small intestine co-express known stem cell markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with the frequency of CD24(LO)CD44(HI) cancer-initiating cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI) and dye efflux(HI) cells, and increasing Oct1 increases the proportion of ALDH(HI) cells. Normal ALDH(HI) cells harbor elevated Oct1 protein but not mRNA levels. Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes hematopoietic stem cell engraftment potential in competitive and serial transplants. In addition to previously described Oct1 transcriptional targets, we identify four Oct1 targets associated with the stem cell phenotype. Cumulatively, the data indicate that Oct1 regulates normal and cancer stem cell function.

• Authors: Jessica Maddox, Arvind Shakya, Samuel South, Dawne Shelton, Jared N Andersen, Stephanie Chidester, Jinsuk Kang, Keith M Gligorich, David A Jones, Gerald J Spangrude, Bryan E Welm, Dean Tantin
• Journal: PLoS genetics (PLoS Genet) Vol. 8 Issue 11 Pg. e1003048 ( 2012) ISSN: 1553-7404 [Electronic] United States
• PMID: 23144633 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• CD24 Antigen
• Hyaluronan Receptors
• Organic Cation Transporter 1
• RNA, Messenger
• Aldehyde Dehydrogenase

Topics

• Aldehyde Dehydrogenase (genetics, metabolism)
• Biomarkers (metabolism)
• CD24 Antigen (metabolism)
• Colon (cytology, metabolism)
• Gene Expression Regulation, Neoplastic
• HeLa Cells
• Humans
• Hyaluronan Receptors (metabolism)
• Intestine, Small (cytology, metabolism)
• Neoplastic Stem Cells (cytology, metabolism)
• Organic Cation Transporter 1 (genetics, metabolism)
• Phenotype
• RNA, Messenger (metabolism)
• Stem Cells (cytology, metabolism)