HIF-1 recruits NANOG as a coactivator for TERT gene transcription in hypoxic breast cancer stem cells.

Breast cancer stem cells (BCSCs) play essential roles in tumor formation, drug resistance, relapse, and metastasis. NANOG is a protein required for stem cell self-renewal, but the mechanisms by which it performs this function are poorly understood. Here, we show that hypoxia-inducible factor 1? (HIF-1?) is required for NANOG-mediated BCSC ...
enrichment. Mechanistically, NANOG is recruited by HIF-1 to cooperatively activate transcription of the TERT gene encoding the telomerase reverse transcriptase that maintains telomere length, which is required for stem cell self-renewal. NANOG stimulates HIF-1 transcriptional activity by recruitment of the deubiquitinase USP9X, which inhibits HIF-1? protein degradation, and by stabilizing HIF-1? interaction with the coactivator p300, which mediates histone acetylation. Our results delineate a cooperative transcriptional mechanism by which HIF-1 and NANOG mediate BCSC self-renewal.
Mesh Terms:
Breast Neoplasms, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Nanog Homeobox Protein, Neoplasm Recurrence, Local, Neoplastic Stem Cells, Telomerase
Cell Rep
Date: Dec. 28, 2020
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