Molecular mechanism of eIF2gamma in Lung cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15018
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KURIMOTO Ryota 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (10753957)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: RNA / eIF2gamma / 肺癌

Outline of Final Research Achievements

By suppressing eIF2gamma by siRNA, the phosphorylation of eIF2a and its downstream factors (ATF-4, CHOP) was promoted at the protein level, and the tumor growth of lung cancer cell lines was suppressed. When knockdown cell lines were generated by shRNA and the tumor growth ability was examined by mouse Xenograft model, suppression of tumor growth ability was observed in the subcutaneous transplantation model. In addition, they have the HA sequence of eIF2gamma-established using the Cas9 method. In addition, knockout mouse eIF2s3y, which is a homologue in mice, was created using the CRISPR-Cas9 method, and it was confirmed that spermatogenesis was strongly suppressed. Confirmed that the current translation. Therefore, conditions of ribosomal footprinting are being studied using established cells.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究の特色は、腫瘍の治療として翻訳機能を直接標的としている点である。eIF2γを抑制することで、直接タンパク質翻訳を抑制する効果とeIF2αリン酸化抑制の解除による間接的効果の２つの効果によって、効率よく腫瘍増殖の抑制が期待される。実際、eIF2γの抑制により、click-it反応を用いた系においてタンパク質合成全体の抑制が確認され、さらにeIF2αのリン酸化抑制の解除が確認された。本研究は、肺癌のみならず難治とされる他の悪性腫瘍の新規治療戦略にもつながり、悪性腫瘍の研究に大きく貢献できると考えられる。