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World J Gastroenterol. Oct 14, 2014; 20(38): 13756-13766
Published online Oct 14, 2014. doi: 10.3748/wjg.v20.i38.13756
Rho/ROCK signaling in motility and metastasis of gastric cancer
Tasuku Matsuoka, Masakazu Yashiro
Tasuku Matsuoka, Masakazu Yashiro, Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Author contributions: Matsuoka T and Yashiro M designed this review; Matsuoka T wrote manuscript and Yashiro M edited manuscript.
Supported by KAKENHI Grant-in-Aid for Scientific Research, No. 23390329; and the National Cancer Center Research and Development Fund, No. 23-A-9
Correspondence to: Masakazu Yashiro, MD, Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. m9312510@med.osaka-cu.ac.jp
Telephone: +81-6-66453838 Fax: +81-6-66466450
Received: October 28, 2013
Revised: April 21, 2014
Accepted: June 12, 2014
Published online: October 14, 2014
Abstract

Gastric cancer is one of the most frequent and lethal malignancies worldwide because of high frequency of metastasis. Tumor cell motility and invasion play fundamental roles in cancer metastasis. Recent studies have revealed that the Rho/Rho-associated protein kinases (ROCK) pathway plays a critical role in the regulation of cancer cell motility and invasion. In addition, the Rho/ROCK pathway plays important roles in invasion and metastasis on the basis of its predominant function of cell cytoskeletal regulation in gastric cancer. According to the current understanding of tumor motility, there are two modes of tumor cell movement: mesenchymal and amoeboid. In addition, cancer cell movement can be interchangeable between the mesenchymal and amoeboid movements under certain conditions. Control of cell motility through the actin cytoskeleton creates the potential for regulating tumor cell metastasis. In this review we discuss Rho GTPases and ROCK signaling and describe the mechanisms of Rho/ROCK activity with regard to motility and metastasis in gastric cancer. In addition, we provide an insight of the therapeutic potential of targeting the Rho/ROCK pathway.

Keywords: RhoGTPases, Rho-associated protein kinases, Gastric cancer, Motility, Metastasis

Core tip: Gastric cancer is one of the main causes of cancer-associated death in the worldwide. The poor prognosis associated with gastric cancer is mainly related to metastasis and cell motility is vital for several steps involved in the metastasis. Rho GTPases could affect cancer progression including cytoskeletal dynamics. This study aimed at gaining further insight into the mechanism of Rho/Rho-associated protein kinases pathway mediated gastric cancer metastasis, particularly with regard to cell movement.