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

Gang Cen; Hong-Hua Ding; Bin Liu; Wei-Dong Wu

doi:10.1007/s13277-014-2104-9

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

Tumour Biol. 2014 Sep;35(9):8633-8. doi: 10.1007/s13277-014-2104-9. Epub 2014 May 28.

Authors

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

Affiliation

¹ Department of General Surgery, The First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, 200080, People's Republic of China.

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

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.

Publication types

Retracted Publication

MeSH terms

Binding Sites / genetics
Blotting, Western
Cell Line, Tumor
Cell Movement*
Cortactin / genetics
Cortactin / metabolism*
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Extracellular Signal-Regulated MAP Kinases / metabolism
F-Box Proteins / genetics
F-Box Proteins / metabolism*
Flavonoids / pharmacology
Humans
Mutation
Phosphorylation
Proteasome Endopeptidase Complex / metabolism
Protein Binding
Protein Kinase Inhibitors / pharmacology
Proteolysis / drug effects
RNA Interference
Serine / genetics
Serine / metabolism
Stomach Neoplasms / genetics
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
Ubiquitin-Protein Ligase Complexes
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism*
Ubiquitination*

Substances

CTTN protein, human
Cortactin
F-Box Proteins
FBXL5 protein, human
Flavonoids
Protein Kinase Inhibitors
Serine
Ubiquitin-Protein Ligase Complexes
Ubiquitin-Protein Ligases
Extracellular Signal-Regulated MAP Kinases
Proteasome Endopeptidase Complex
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one