Targeting VPS41 induces methuosis and inhibits autophagy in cancer cells

Published: 12 January 2023| Version 1 | DOI: 10.17632/yx4cfz6zr3.1
Yue Liu


This dataset contains original western blots and full MS data , related to this work whose abstract is as follows: The homotypic fusion and vacuole protein sorting (HOPS) complex mediates membrane trafficking involved in endocytosis, autophagy, lysosome biogenesis and phagocytosis. Defects in HOPS subunits are associated with various forms of cancer, but their potential as drug targets has rarely been examined. Here, we identified vacuolar protein sorting-associated protein 41 homolog (VPS41), a subunit of the HOPS complex, as a target of methyl 2,4-dihydroxy-3-(3-methyl-2-butenyl)-6-phenethylbenzoate (DMBP), a natural small molecule with preferable anticancer activity. DMBP induced methuosis and inhibited autophagic flux in cancer cells by inhibiting the function of VPS41, leading to the restrained fusion of late endosomes and autophagosomes with lysosomes. Moreover, DMBP effectively inhibited metastasis in a mouse metastatic melanoma model. Collectively, the current work revealed that targeting VPS41 would provide a new method of inhibiting cancer proliferation through methuosis.



Shandong University


Cancer, Cell Death, Target Identification