Literature DB >> 24867096

FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate gastric cancer cell migration.

Gang Cen1, Hong-Hua Ding, Bin Liu, Wei-Dong Wu.   

Abstract

Cortactin, an actin-interacting protein, is implicated in cytoskeletal architecture and often amplified in several types of cancer including gastric adenocarcinomas. Downregulation of cortactin decreases cell migration and invasion. However, how to regulate cortactin in gastric cancer remains largely unknown. Here, we report that FBXL5 interacts with and targets cortactin for ubiquitylation and subsequent proteasomal degradation. Furthermore, we showed that FBXL5-induced cortactin degradation is mediated by extracellular regulated signal kinase (ERK). Serine phosphorylation sites mutant, cortactinS405A/S418A, prevent FBXL5-induced cortactin degradation. Moreover, CortactinS405A/S418A exhibited stronger effects in promoting gastric cancer cell migration when compared to wild-type cortactin. Taken together, our data suggested a novel molecular mechanism for the negative regulation of cortactin by FBXL5 in gastric cancer cells migration.

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Year:  2014        PMID： 24867096     DOI： 10.1007/s13277-014-2104-9

Source DB:  PubMed          Journal:  Tumour Biol        ISSN： 1010-4283


  20 in total

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