Validation of the PIP3 Threshold Model in Melanoma Progression and Resistance to Treatment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08288
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Nippon Medical School (2019-2020); Akita University (2018)
• Principal Investigator: Osada Shin-Ichi 日本医科大学, 医学部, 准教授 (00244484)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: メラノーマ / イノシトールリン脂質 / INPP4B / PTEN / PI3K経路 / 免疫チェックポイント阻害薬

Outline of Final Research Achievements

Intracellular PIP3, one of the inositol phospholipids, is closely related to carcinogenesis. In this study, we used melanoma mice lacking the Inpp4b gene, which was recently found to be involved in PIP3 production, to examine whether the malignancy of melanoma becomes more progressive as the amount of intratumoral PIP3 increases (PIP3 threshold model). The results suggest that Inpp4b heterozygous deleted melanomas are more malignant and resistant to treatment than Inpp4b homozygous deleted melanomas.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究によりPIP3閾値モデルがメラノーマにも一部当てはまることが示唆された。腫瘍内PIP3量の増加は免疫チェックポイント阻害薬に対する感受性を低めることが報告されており、Inpp4bがメラノーマにおいてもPIP3量の増加に関わることを明らかにした本研究は、今後メラノーマの悪性度、治療抵抗性のメカニズムの解明につながる。