title: Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck squamous cell carcinoma.
abstract: Expression of the protein deacetylase SIRT1 is associated with either poor or favorable prognosis in cancer patients, depending on the cancer type. In head and neck squamous cell carcinoma (HNSCC), SIRT1 expression is associated with favorable prognosis. However, the molecular mechanism underlying the tumor-suppressive function of SIRT1 in HNSCC is unknown. SIRT1 promotes differentiation in epithelial cells; therefore, we investigated whether SIRT1 promotes differentiation in HNSCC cells by studying the correlations between the expression of SIRT1 and several genes implicated in stemness or differentiation in HNSCC-derived cell lines. Our results suggest that SIRT1 does not contribute to differentiation in HNSCC cells. RNA interference-mediated reduction of SIRT1 revealed that SIRT1 supports the expression of TAp63, which has been implicated in tumor suppression, in addition to epithelial differentiation. A positive correlation was observed between SIRT1 and TAp63 expression in HNSCC tissues, as determined by quantitative reverse transcription-polymerase chain reaction analysis of RNA extracted from formalin-fixed paraffin-embedded biopsy samples. Together, these results suggest that although SIRT1 does not regulate differentiation of HNSCC cells, it functions as a tumor suppressor in HNSCC by supporting the transcription of tumor-suppressive TAp63. This finding supports the notion that SIRT1-activating drugs could be useful for the treatment of HNSCC.
authors.affiliation: Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan. kei@gancen.asahi.yokohama.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kikuchi
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Noguchi
authors.affiliation: Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Kasajima
authors.affiliation: Molecular Pathology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hoshino
authors.affiliation: Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Koshikawa
authors.affiliation: Department of Head and Neck Cancer, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kubota
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.affiliation: Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-8515, Japan.|School of Health Sciences, Tokyo University of Technology, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Cell differentiation; Head and neck squamous cell carcinoma; Prognosis; SIRT1; TAp63; Tumor suppression