Open AccessFOXM1 regulates glycolysis in nasopharyngeal carcinoma cells through PDK1
Author(s) -
Yang Qing,
Wu Fang,
Zhang Yong,
Wang Rensheng
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17413
Subject(s) - foxm1 , glycolysis , lactate dehydrogenase a , cancer research , nasopharyngeal carcinoma , microbiology and biotechnology , biology , transcription factor , oncogene , phosphorylation , pkm2 , chemistry , pyruvate kinase , biochemistry , cell cycle , gene , medicine , metabolism , radiation therapy
The transcription factor forkhead box M1 (FOXM1) is a well‐known proto‐oncogene that plays a significant role in the pathogenesis of various human cancers. However, the regulatory role and underlying mechanisms of FOXM1 in nasopharyngeal carcinoma (NPC) metabolism remain unclear. We demonstrated that FOXM1 could positively regulate glycolysis in NPC cells. Functional studies have shown that pyruvate dehydrogenase kinase 1 (PDK1) is involved in FOXM1‐regulated lactate production, ATP generation and glycolysis. FOXM1 binds directly to the PDK1 promoter region and increases the expression of PDK1 at the transcriptional level, leading to the phosphorylation of pyruvate dehydrogenase (PDH) at serine 293, inhibiting its activity. Knocking down FOXM1 using specific short hairpin RNAs (shRNAs) can significantly decrease glycolysis and the expression of PDK1 in NPC cells. Furthermore, microenvironmental factors can increase the expression of FOXM1 by regulating hypoxia‐inducible factor 1α (HIF‐1α) expression. Clinical data and in vivo studies confirmed the positive roles of FOXM1/PDK1 in NPC proliferation and progression. In conclusion, our findings revealed that FOXM1 regulates glycolysis and proliferation of NPC through PDK1‐mediated PDH phosphorylation. Therefore, targeting the FOXM1‐PDK1 axis may be a potential therapeutic strategy for NPC.