SOX4-SMARCA4 complex promotes glycolysis-dependent TNBC cell growth through transcriptional regulation of Hexokinase 2.

Autor:	Khanna P; Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA., Mehta R; Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA., Mehta GA; Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA., Bhatt V; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.; Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.; Department of Chemical Biology, Rutgers Ernest Mario School of Pharmacy, Piscataway, New Jersey 08854., Guo JY; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.; Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.; Department of Chemical Biology, Rutgers Ernest Mario School of Pharmacy, Piscataway, New Jersey 08854., Gatza ML; Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA.; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 13. Date of Electronic Publication: 2023 Sep 13.
DOI:	10.1101/2023.09.10.557071
Abstrakt:	Tumor cells rely on increased glycolytic capacity to promote cell growth and progression. While glycolysis is known to be upregulated in the majority of triple negative (TNBC) or basal-like subtype breast cancers, the mechanism remains unclear. Here, we used integrative genomic analyses to identify a subset of basal-like tumors characterized by increased expression of the oncogenic transcription factor SOX4 and its co-factor the SWI/SNF ATPase SMARCA4. These tumors are defined by unique gene expression programs that correspond with increased tumor proliferation and activation of key metabolic pathways, including glycolysis. Mechanistically, we demonstrate that the SOX4-SMARCA4 complex mediates glycolysis through direct transcriptional regulation of Hexokinase 2 (HK2) and that aberrant HK2 expression and altered glycolytic capacity are required to mediate SOX4-SMARCA4-dependent cell growth. Collectively, we have defined the SOX4-SMARCA4-HK2 signaling axis in basal-like breast tumors and established that this axis promotes metabolic reprogramming which is required to maintain tumor cell growth.
Databáze:	MEDLINE
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