Menin-mediated Repression of Glycolysis in Combination with Autophagy Protects Colon Cancer Against Small-molecule EGFR Inhibitors.

ABSTRACT: Menin serves both tumor suppressor and promoter roles in a highly tumor-specific manner. In colorectal cancer, menin is overexpressed and plays a critical role in regulating transcription of SKP2, and combined treatment with a menin inhibitor and small-molecule EGFR inhibitor (EGFRi) leads to synergistic killing of colorectal cancer cells. However, the full spectrum of menin function in colorectal cancer remains uncertain. Herein, we demonstrate that menin inhibition increases glycolysis in colorectal cancer cells. This menin inhibitor-induced increase in glycolysis occurs in an mTOR-independent manner and enhances the sensitivity of colorectal cancer cells to EGFRis. In addition, we show that EGFRis induce autophagy in colorectal cancer cells, which is important for cell survival in the s

SUBMITTER: Katona BW 

PROVIDER: S-EPMC7921201 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature