Molecular mechanisms of cancer metastasis induced by disrupting the WNK kinase mediated cytosolic Cl- homeostasis

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460297
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Miyazaki Hiroaki 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (30360027)
• Co-Investigator(Kenkyū-buntansha): MARUNAKA Yoshinori 京都府立医科大学, 大学院医学研究科, 教授 (00127036) ; NIISATO Naomi 京都学園大学, 健康医療学部, 教授 (00237645) ; HOSOGI Shigekuni 京都府立医科大学, 大学院医学研究科, 講師 (30433254)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 細胞内Cl-濃度 / 細胞増殖 / 細胞接着 / 細胞運動

Outline of Final Research Achievements

A malignant tumor is a serious health problem because cancer cells can spread to distant parts of the body, so-called metastasis. Since metastasis is the most common cause of death from cancer, this process is an important therapeutic target. However, the molecular mechanisms of the metastasis are not fully understood. Our recent studies show that the cytosolic Cl- plays important roles in fundamental cellular functions. Thus, we investigated the effect of cytosolic Cl- concentration ([Cl-]c) on the cell proliferation, the cell migration and the cell invasion in several gastrointestinal tumor cell lines. Our study indicates that cytosolic Cl- is a key factor regulating expression of cell adhesion molecules, including E-cadherin and integrins and that cytosolic Cl- regulates WNK and Src kinase signal cascades involved in tumor proliferation, migration and invasion. These results strongly suggest that changes of [Cl-]c would play important roles in cancer development and progression.

Free Research Field

細胞生理学