Cancer progression through Trop-2 phosphorylation

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K14998
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kyoto Sangyo University
• Principal Investigator: MORI Yugo 京都産業大学, 総合生命科学部, 講師 (00780785)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 癌 / 細胞移動・転移 / 細胞間接着 / 発現制御機構

Outline of Final Research Achievements

Trophoblast cell surface antigen 2 (Trop-2) is highly expressed in a variety of epithelial cancer cells, and its increased expression in tumor tissues is correlated with biological aggressiveness and poor survival of patients with various cancer types. However, Trop-2 is known to be widely expressed in normal tissues and involved in function of tight junction through its interaction with tight junction component claudin-7. Thus, the function of Trop-2 remains obscure. Here, we focused on not only quantitative but also qualitative change, i.e., phosphorylation of Trop-2. We revealed that Trop-2 was phosphorylated by PKCα/δ, and that chemical inhibitor of PKCα/δ reduced cell motility.
Our results suggest that Trop-2 phosphorylation leads to the dysfunction of cell-cell adhesion.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

Trop-2の量的な変化に伴う癌悪性化との関連性の解析は、今までも多くの研究がなされているが、本研究は、Trop-2の量的な変化だけではなく、質的な変化が、癌の悪性化機構に関与していることを示唆する初めての報告となる。これは今後、癌におけるTrop-2の機能を解析していく上で有用な知見になり得ると考えられ、またTrop-2のリン酸化レベルの測定は、癌の悪性化を評価する新たな指標となり得る可能性を示すものである。