Expression and role of LRRC8A in esophageal squamous cell carcinoma.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08628
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Harada Kyoichi 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80804822)
• Co-Investigator(Kenkyū-buntansha): 大辻 英吾 京都府立医科大学, 医学(系)研究科(研究院), 教授 (20244600) ; 塩崎 敦 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40568086)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 食道癌

Outline of Final Research Achievements

The depletion of LRRC8A using siRNA decreased cell proliferation and cellular movement, and promoted the induction of apoptosis in human esophageal squamous cell carcinoma (ESCC) cells. The microarray analysis revealed that G1/S checkpoint regulation, PI3K/AKT signaling, MMP, and integrin signaling-related genes, such as p21, p27, E2F7, AKT, Bcl2, MMP1 and ITGAvα, were up- or down-regulated in LRRC8A-depleted cells. An immunohistochemical analysis revealed a relationship between strong LRRC8A expression and a poor prognosis in ESCC patients. Further, hypotonic solution at low temperature increased initial water influx via activation of AQP5 and decreased Cl- efflux via inhibition of LRRC8A. These results provide an insight into the role of LRRC8A as a mediator and/or a biomarker for ESCC. Further, Low temperature enhances hypotonicity-induced cytocidal effects, which may contribute to development of a novel lavage method to reduce peritoneal recurrence.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

LRRC8Aが食道扁平上皮癌組織において高発現し、そのRNA干渉が癌細胞に抑制効果を示すことを新たに見出した。LRRC8Aのp21、p27、E2F7やMMP、Integrinを介する新たな腫瘍進展制御機構や、予後因子としての意義を明らかにし、バイオマーカーや治療標的としての可能性を示した。また、温度変化がLRRC8Aの発現変化を介してRVDを制御する機構を解明し、LRRC8Aや温度制御を利用した、低浸透細胞破壊療法への応用が期待される。