RRC ID 72356
Author Saji T, Nishita M, Ikeda K, Endo M, Okada Y, Minami Y.
Title c-Src-mediated phosphorylation and activation of kinesin KIF1C promotes elongation of invadopodia in cancer cells.
Journal J Biol Chem
Abstract Invadopodia on cancer cells play crucial roles in tumor invasion and metastasis by degrading and remodeling the surrounding extracellular matrices and driving cell migration in complex 3D environments. Previous studies have indicated that microtubules (MTs) play a crucial role in elongation of invadopodia, but not their formation, probably by regulating delivery of membrane and secretory proteins within invadopodia. However, the identity of the responsible MT-based molecular motors and their regulation has been elusive. Here, we show that KIF1C, a member of kinesin-3 family, is localized to the tips of invadopodia and is required for their elongation and the invasion of cancer cells. We also found that c-Src phosphorylates tyrosine residues within the stalk domain of KIF1C, thereby enhancing its association with tyrosine phosphatase PTPD1, that in turn activates MT-binding ability of KIF1C, probably by relieving the autoinhibitory interaction between its motor and stalk domains. These findings shed new insights into how c-Src signaling is coupled to the MT-dependent dynamic nature of invadopodia and also advance our understanding of the mechanism of KIF1C activation through release of its autoinhibition.
Volume 298(7)
Pages 102090
Published 2022-7-1
DOI 10.1016/j.jbc.2022.102090
PII S0021-9258(22)00531-2
PMID 35654143
PMC PMC9234240
MeSH Cell Line, Tumor Genes, src* Humans Kinesins* / genetics Microtubules / metabolism Neoplasm Invasiveness* Phosphorylation Podosomes* / metabolism Protein Tyrosine Phosphatases, Non-Receptor Tyrosine / metabolism
IF 4.238
DNA material Genome Network Project Human cDNA Clone IRAK047K20 (HGY019060)