Small GTP-binding protein Rho stimulates the actomyosin system, leading to invasion of tumor cells

Kiyoko Yoshioka, Fumio Matsumura, Hitoshi Akedo, Kazuyuki Itoh

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

We have shown previously that Rho plays a pivotal role in 1-oleoyl- lysophosphatidic acid (LPA)-dependent invasion of rat hepatoma cells (MM1). Herein we made stable transfectants of MM1 expressing active and Botulinum exoenzyme C3 (C3)-sensitive (Val14), or active and C3-insensitive (Val14/Ile41) forms of human RhoA. Both transfectants showed greatly promoted invasive ability in vitro in the absence of LPA as well as in vivo, adherence to the dish with scattered shape, and enhanced phosphorylation level of 20-kDa myosin light chain (MLC20). A specific MLC kinase inhibitor (KT5926) could inhibit their invasion and the phosphorylation level of MLC20. Stable active RhoA transfectants of W1 cells (low invasive counterpart of MM1) also demonstrated promoted invasive ability in vitro and in vivo, and enhanced phosphorylation level of MLC20. C3 treatment inhibited the invasiveness of the Val14 RhoA transfectant but not that of the Val14[Ile41 RhoA transfectant. LPA enhanced the invasiveness of both transfectants, and this enhancement was abolished by the C3 treatment. These results suggested that 1) the Rho signaling pathway and actomyosin system were linked in the transmigration of tumor cells, and 2) expressed active RhoA enhanced LPA-induced tumor cell invasion via the activation of endogenous RhoA pathway, indicating a positive feedback mechanism in the activation of RhoA.

Original languageEnglish (US)
Pages (from-to)5146-5154
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number9
DOIs
StatePublished - Feb 27 1998

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Actomyosin
rho GTP-Binding Proteins
Phosphorylation
Tumors
Cells
Neoplasms
Chemical activation
Myosin Light Chains
Rats
Hepatocellular Carcinoma
Phosphotransferases
Feedback
lysophosphatidic acid
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Yoshioka, Kiyoko ; Matsumura, Fumio ; Akedo, Hitoshi ; Itoh, Kazuyuki. / Small GTP-binding protein Rho stimulates the actomyosin system, leading to invasion of tumor cells. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 9. pp. 5146-5154.
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Small GTP-binding protein Rho stimulates the actomyosin system, leading to invasion of tumor cells. / Yoshioka, Kiyoko; Matsumura, Fumio; Akedo, Hitoshi; Itoh, Kazuyuki.

In: Journal of Biological Chemistry, Vol. 273, No. 9, 27.02.1998, p. 5146-5154.

Research output: Contribution to journalArticle

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AU - Yoshioka, Kiyoko

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