Citations : Bacterial type III effector protein HopQ inhibits melanoma motility through autophagic degradation of vimentin
Dated: Apr 14, 2020
Publication Name: Cell Death and Disease
Malignant melanoma is a fatal disease that rapidly spreads to the whole body. Treatments have limited efficiency owing to drug resistance and various side effects. Pseudomonas syringae pv. tomato (Pto) is a model bacterial pathogen capable of systemic infection in plants. Pto injects the effector protein HopQ into the plant cytosol via a type III secretion machinery and suppresses the host immunity. Intriguingly, host plant proteins regulated by HopQ are conserved even in humans and conferred in tumor metastasis. Nevertheless, the potential for HopQ to regulate human cancer metastasis was unknown. In this study, we addressed the suitability of HopQ as a possible drug against melanoma metastasis. In melanoma cells, overexpressed HopQ is phosphorylated and bound to 14-3-3 through its N-terminal domain, resulting in stronger interaction between HopQ and vimentin. The binding of HopQ to vimentin allowed for degradation of vimentin via p62-dependent selective autophagy. Attenuation of vimentin expression by HopQ inhibited melanoma motility and in vivo metastasis. These findings demonstrated that HopQ directly degraded vimentin in melanoma cells and could be applied to an inhibitor of melanoma metastasis.
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Contributors: Seung-Ho Park, Sung-Jin Yoon, Song Choi, Jun-Seob Kim, Moo-Seung Lee, Seon-Jin Lee, Sang-Hyun Lee, Jeong-Ki Min, Mi-Young Son, Choong-Min Ryu, Jiyun Yoo & Young-Jun Park