Role of INPP4B in melanoma development: possible effects of 3-BP as promising anticancer drug

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461679
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Akita University
• Principal Investigator: MANABE MOTOMU 秋田大学, 医学(系)研究科(研究院), 教授 (30138309)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: INPP4B / PTEN / PI3K / メラノーマ / 糖代謝

Outline of Final Research Achievements

INPP4B negatively regulates pi3-kinase signaling and is a tumor suppressor in some types of cancers. However, the role of INPP4B in the development of melanoma remains unclear. We therefore sought to investigate the tumor suppressive functions of INPP4B in vivo in knock-out KO mouse models. Here, we show that (1) Inpp4b null mice do not develop the tumorigenic phenotype of Pten haploinsufficient mice, (2) Inpp4b null mice develop the tumorigenic phenotype of Pten null mice.
Furthermore, to develop a novel therapeutic approach for melanoma, we studied the cytotoxic effects of an glycolysis　inhibitor 3-bromopyruvate (3-BP) in both in vivo and in vitro mouse melanoma model. 3-BP induced cell death in melanoma cells and increased intracellular reactive oxygen species.Interestingly, 3-BP also induced cell death in colony forming cells and slow cycling cells. Taken together, these findings provided the evidences that 3-BP is a promising anticancer drug.

Free Research Field

皮膚科学