|Title:||PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization||Authors:||Li, Meng Yen
Lin, Yu Ling
Chang, Ya Min
Peng, Wen Hsin
Wu, Han Chung
Wu, Chien Hsun
Chen, Guang Chao
© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Cancer cell migration plays a crucial role during the metastatic process. Reversible tyrosine phosphorylation by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) have been implicated in the regulation of cancer cell migration and invasion. However, the underlying mechanisms have not been fully elucidated. Here, we show that depletion of the FERM and PDZ domain-containing protein tyrosine phosphatase PTPN3 enhances lung cancer cell migration/invasion and metastasis by promoting actin filament assembly and focal adhesion dynamics. We further identified Src and DAAM1 (dishevelled associated activator of morphogenesis 1) as interactors of PTPN3. DAAM1 is a formin-like protein involved in the regulation of actin cytoskeletal remodeling. PTPN3 inhibits Src activity and Src-mediated phosphorylation of Tyr652 on DAAM1. The tyrosine phosphorylation of DAAM1 is essential for DAAM1 homodimer formation and actin polymerization. Ectopic expression of a DAAM1 phosphodeficient mutant inhibited F-actin assembly and suppressed lung cancer cell migration and invasion. Our findings reveal a novel mechanism by which reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulates actin dynamics and lung cancer invasiveness.
cell protein; cytoskeleton protein; dishevelled associated activator of morphogenesis 1 protein; F actin; four point 1 ezrin radixin and moesin homology protein; homodimer; mutant protein; non receptor protein tyrosine phosphatase 3; protein tyrosine kinase; tyrosine; unclassified drug; actin; actin binding protein; DAAM1 protein, human; non receptor protein tyrosine phosphatase 3; protein p21; PTPN3 protein, human; Rho guanine nucleotide binding protein; actin filament; actin polymerization; animal experiment; animal model; animal tissue; Article; cancer cell; cancer inhibition; cell invasion; cell migration; controlled study; enzyme activity; enzyme inhibition; focal adhesion; human; human cell; lung cancer; metastasis; molecular dynamics; mouse; nonhuman; priority journal; protein assembly; protein expression; protein phosphorylation; protein protein interaction; regulatory mechanism; lung tumor; metabolism; pathology; physiology; polymerization; tumor invasion; Actins; Focal Adhesions; Humans; Lung Neoplasms; Microfilament Proteins; Neoplasm Invasiveness; Polymerization; Protein Tyrosine Phosphatase, Non-Receptor Type 3; Proto-Oncogene Proteins p21(ras); rho GTP-Binding Proteins
|Appears in Collections:||生化科學研究所|
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