Novel cancer therapeutic target, epithelial membrane protein 1 (EMP1), investigation of the molecular mechanism inducing invasion and metastasis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08657
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Akio Shimizu 滋賀医科大学, 医学部, 助教 (30769279)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: がん / 浸潤 / 転移 / EMP1

Outline of Final Research Achievements

Metastatic cancer is frequently led to fatality. Thus, understanding of the underlying mechanism is important to reduce it. The expression of epithelial membrane protein 1 (EMP1) was upregulated in prostate cancer cells by contacting with surrounding stroma cells. EMP1 has four transmembrane domains. Overexpression of EMP1 in prostate cancer, LNCaP cells (EMP1-LNCaP cells) enhanced invasiveness, which was also observed in other types of cancer cells. In in vivo analysis, EMP1-LNCaP cells implanted in the prostate metastasized to lymph nodes and the lung but the parental LNCaP did not. Next, copine-III was identified by usage of tandem mass spectrometry as a novel molecule binding to the intracellular region of EMP1. The EMP1-copine-III complex induced the signal via Src, Vav2, and Rac1, leading to the enhanced cancer cell migration and invasion. As clinical implications, increased EMP1 expression was observed in the samples from prostate cancer patients with higher Gleason scores.

Free Research Field

血管新生

Academic Significance and Societal Importance of the Research Achievements

本研究は、がん細胞と正常細胞の相互作用によってEMP1の発現が上昇することを明らかにし、浸潤・転移への寄与を明らかにした点に新規の学術的意義がある。EMP1は悪性度の高いがん患者検体においてその発現が上昇していたことを明らかにしたが、EMP1は細胞膜タンパク質であり、外部から抗体や薬剤などでその作用を阻害しやすいことは臨床応用へ進む上で大きな利点である。本研究の成果から、がんの治療標的あるいは分子マーカーとしてEMP1 は有用である可能性が示された。