Study of unconventional protein secretion in cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07621
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: YAMADA Kohji 東京慈恵会医科大学, 医学部, 講師 (90570979)
• Co-Investigator(Kenkyū-buntansha): 吉田 彩舟 東京慈恵会医科大学, 医学部, 講師 (40772744) ; 立花 利公 東京慈恵会医科大学, 医学部, 教授 (80163476)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: タンパク質の多機能性 / 型破り分泌

Outline of Final Research Achievements

We have previously found that importin α1 and protein kinase C delta (PKCδ) are released from proliferating cancer cells. In this period, we have made two major discoveries. First, we found that PKCδ is highly detected in the serum of patients with hepatocellular carcinoma, while it is low in the serum of healthy subjects and patients with chronic hepatitis. In particular, it is detected in patients with very early-stage cancer, suggesting that it may be a novel biomarker. Second is the elucidation of the secretion mechanism. Using PKCδ as a model, we used the proximity labeling method to analyze the secretory pathway of PKCδ and found a vesicular trafficking pathway originating from the endoplasmic reticulum. The characteristics of the unconventional secretion of this cytoplasmic protein found in liver cancer include: 1) it occurs under normal culture conditions, 2) it originates from the endoplasmic reticulum, and 3) it contributes to tumorigenesis.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

通常、腫瘍組織の外液成分における細胞質タンパク質のほとんどは細胞膜破壊による漏出と考えられてきた。一方で本研究により、細胞質タンパク質の一部は分泌され、肝がん特異性が高く、腫瘍形成に積極的に寄与することを突き止めた。特に、プロテインキナーゼCデルタ（PKCδ）に関しては早期診断用の血液バイオマーカーになる可能性があるのみならず、細胞外PKCδまたはその分泌機構が治療標的になる可能性が高く、肝がん医療における臨床的意義は大きい。