Subcellular localization and biological functions of SIRT1 in head and neck squamous cell carcinoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 24593043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kanagawa Cancer Center Research Institute
• Principal Investigator: KIKUCHI Keiji 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), その他部局等, その他 (90372094)
• Co-Investigator(Kenkyū-buntansha): NOGUCHI Akira 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), がん生物学部, 研究員 (10456395) ; TAKANO Yasuo 地方独立行政法人神奈川県立病院機構, 神奈川県立がんセンター(臨床研究所), 所長 (60142022) ; NOGUCHI Makoto 富山大学, 大学院医学薬学研究部, 教授 (50208328)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: SIRT1 / 頭頸部癌 / TAp63

Outline of Final Research Achievements

Participation of protein deacetylase SIRT1 to cancer initiation and progression depends on the context, including cancer types and subcellular localization of SIRT1. In head and neck squamous cell carcinoma (HNSCC), we found that high SIRT1 expression in nuclei predicts favorable prognosis in patients, while it in cytoplasm accompanies malignancy. To know the roles of SIRT1 in HNSCC, we investigated what genes are regulated by SIRT1 in HNSCC cells and found that SIRT1 contributes to transcription of the TAp63 gene, a member of TP53 family and implicated in tumor suppression. As TAp63 suppresses metastasis, we examined the effect of expression of SIRT1 carrying mutations in nuclear localization signals on cell invasion in HNSCC-derived cells. No significant changes in invasive activity of the cells upon cytoplasmic expression of EGFP-mutated SIRT1 was observed, suggesting that cytoplasmic SIRT1 participates in malignancy through cellular processes other than cell invasion.

Free Research Field

分子細胞生物学