MYCRegulates theHIF2αStemness Pathway viaNanogandSox2to Maintain Self-Renewal in Cancer Stem Cells versus Non-Stem Cancer Cells
Abstract
Cancer stem cells (CSC) maintain both undifferentiated self-renewing CSCs and differentiated, non-self-renewing non-CSCs through cellular division. However, molecular mechanisms that maintain self-renewal in CSCs versus non-CSCs are not yet clear. Here, we report that in a transgenic mouse model of MYC-induced T-cell leukemia, MYC, maintains self-renewal in Sca1+ CSCs versus Sca-1− non-CSCs. MYC preferentially bound to the promoter and activated hypoxia-inducible factor-2α (HIF2α) in Sca-1+ cells only. Furthermore, the reprogramming factors, Nanog and Sox2, facilitated MYC regulation of HIF2α in Sca-1+ versus Sca-1− cells. Reduced expression of HIF2α inhibited the self-renewal of Sca-1+ cells; this effect was blocked through suppression of ROS by N-acetyl cysteine or the knockdown of p53, Nanog, or Sox2. Similar results were seen in ABCG2+ CSCs versus ABCG2− non-CSCs from primary human T-cell lymphoma. Thus, MYC maintains self-renewal exclusively in CSCs by selectively binding to the promoter and activating the HIF2α stemness pathway. Identification of this stemness pathway as a unique CSC determinant may have significant therapeutic implications.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 15, 2019
- Source ID
- 10.1158/0008-5472.can-18-2847
Entities
People
- Amal C. Kataki
- Anupam Sarma
- Arvin M. Gouw
- Bidisha Pal
- Bikul Das
- Dean W Felsher
- Debabrat Baishya
- Gayatri Gogoi
- Hong Li
- Jason R. Gotlib
- Joyeeta Talukdar
- Seema Bhuyan
- Sorra Sandhya
- Sukanya Gayan
Organizations
- Assam Medical College
- Gauhati University
- Indian Institutes of Technology
- National Institutes of Health
- Stanford University
- United States Department of Defense
- University of Massachusetts