Elucidation of the mechanism of oncogenic transformation by Pdcd4 knockdown

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18969
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Mukogawa Women's University
• Principal Investigator: YOSHIKAWA Noriko 武庫川女子大学, 薬学部, 准教授 (40373120)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Pdcd4 / がん化・悪性化

Outline of Final Research Achievements

Programmed cell death 4 (Pdcd4) is a novel tumor suppressor gene which acts as a negative regulator of protein translation and transformation. Pdcd4 expression decreases during carcinogenesis in several human cancer sites. Moreover, the direct targets of Pdcd4 have not been clarified. In order to elucidate whether Pdcd4 inhibits the oncogenic transformation and tumor malignancy, we knocked down Pdcd4 in cells.
We demonstrated that Pdcd4 suppresses the invasive ability of tumor cells through inhibiting MMP-2 secretion and expression of Twist1. Furthermore, we identified that the tumor suppressor Pdcd4 attenuates the translation of delta Np73 mRNA. Delta Np73, an isoform of p73 lacking the NH2-terminal transactivation domain, plays an oncogenic role by interfering with the transcriptional activity of tumor suppressors p53 and TA (full-length transactivating isoform) p73.

Free Research Field

がん転移

Academic Significance and Societal Importance of the Research Achievements

Pdcd4 が細胞の遊走能および浸潤能を抑制すること、その標的分子として、MMP-2 及び Twist1 を見出した。さらに、Pdcd4 が直接翻訳を阻害している標的分子として、ΔNp73 遺伝子を同定した。これまでの臨床研究により Pdcd4 発現レベルは、多種類のがんの進行度・予後の診断に有用であることが報告されている。従って、Pdcd4 の ΔNp73 翻訳抑制を介した細胞のがん化・悪性化抑制機構を解明すれば、新たながん治療法の標的を提示することが出来ると期待される。