Open AccessInvolvement of c‐Src in Carcinoma Cell Motility and Metastasis
Author(s) -
Sakamoto Michiie,
Takamura Masaaki,
Ino Yoshinori,
Miura Ayaka,
Genda Takuya,
Hirohashi Setsuo
Publication year - 2001
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2001.tb01184.x
Subject(s) - proto oncogene tyrosine protein kinase src , lamellipodium , motility , focal adhesion , cancer research , biology , microbiology and biotechnology , pseudopodia , metastasis , tyrosine kinase , cell migration , kinase , chemistry , cell , phosphorylation , actin , signal transduction , cancer , biochemistry , genetics
Carcinoma cells exhibit dysfunction/dysregulation of cell adhesion systems that correlates with their abilities to migrate, invade, and metastasize. Here we show that the tyrosine kinase c‐Src is required for motility and metastasis of two carcinoma cell lines. Adherent KYN‐2 cells having a high level of c‐Src kinase activity become scattered, extend lamellipodia, and exhibit high motility. Expression of a dominant‐negative mutant form of c‐Src caused formation of stress fibers and focal adhesions, and markedly reduced motility. HCT15 cells extended lamellipodia and became scattered in response to lysophosphatidic acid stimulation in parallel with transient activation of c‐Src, which was inhibited by expression of a dominant‐negative mutant form of c‐Src or treatment with a specific Src kinase inhibitor. Furthermore, implantation of dominant‐negative c‐Src trans‐fectants into the peritoneal cavity of SCID mice resulted in reduced peritoneal dissemination compared with control transfectants. These findings indicate that c‐Src activation is critically involved in carcinoma cell migration and metastasis.