AI Article Synopsis
- The HOPS complex plays a key role in various cellular processes like endocytosis and lysosome biogenesis, and defects in its subunits are linked to different cancers.
- Researchers identified VPS41, a subunit of the HOPS complex, as a target for DMBP, a natural compound with promising anticancer properties.
- DMBP was found to induce methuosis and block autophagic activity in cancer cells by affecting VPS41, leading to inhibited cancer cell growth and reduced metastasis in a mouse model.
Article Abstract
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 valuable method of inhibiting cancer proliferation through methuosis.
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| http://dx.doi.org/10.1016/j.chembiol.2023.01.002 | DOI Listing |
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