Possible contributions of heat stress-induced Stat3 activation on abnormality of cancer cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06672
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Youhei Saito 京都薬科大学, 薬学部, 助教 (90411032)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 熱ストレス / Hsp / Stat / 低酸素 / HIF / VEGF

Outline of Final Research Achievements

The stress response contributes to cellular homeostasis by expressing heat shock proteins (Hsp). However, Hsp causes resistance to heat stress and anticancer drugs in cancer cells. In this study, we showed the involvement of Stat3 and Hsp105 in the acquisition of thermotolerance of cancer cells. Since Stat3 activation contributes to cancer cell survival and metastasis, we investigated how heat stress possibly induces enhanced metastatic invasion and epithelial-mesenchymal transition. Cell migration assay and western blot analysis suggested that heat shock increases the number of migrating cells and the involvement of Stat3 phosphorylation in the heat shock-induced cancer cell migration.

Free Research Field

生物系薬学

Academic Significance and Societal Importance of the Research Achievements

本研究により、熱ストレスによるStat3活性化の生理的意義として、Stat3の標的遺伝子の発現を介した温熱耐性獲得、細胞転移能亢進などが示唆された。これらは、癌温熱療法や化学療法における治療の妨げや癌悪性化の可能性を示している。熱ストレスにより活性化したStat3を阻害することは治療効果の向上と副作用の低減に有用であると期待される。