Rho/ROCK signaling in motility and metastasis of gastric cancer

World J Gastroenterol. 2014 Oct 14;20(38):13756-66. doi: 10.3748/wjg.v20.i38.13756.

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: Gastric cancer; Metastasis; Motility; Rho-associated protein kinases; RhoGTPases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Movement* / drug effects
  • Drug Design
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction* / drug effects
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / pathology
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / metabolism*
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • rho-Associated Kinases
  • rho GTP-Binding Proteins