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Erschienen in: Tumor Biology 10/2015

01.10.2015 | Research Article

Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck squamous cell carcinoma

verfasst von: Keiji Kikuchi, Akira Noguchi, Rika Kasajima, Yohei Miyagi, Daisuke Hoshino, Naohiko Koshikawa, Akira Kubota, Tomoyuki Yokose, Yasuo Takano

Erschienen in: Tumor Biology | Ausgabe 10/2015

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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.
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Literatur
9.
Zurück zum Zitat Noguchi A, Li X, Kubota A, Kikuchi K, Kameda Y, Zheng H, et al. SIRT1 expression is associated with good prognosis for head and neck squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115(3):385–92. doi:10.1016/j.oooo.2012.12.013.CrossRefPubMed Noguchi A, Li X, Kubota A, Kikuchi K, Kameda Y, Zheng H, et al. SIRT1 expression is associated with good prognosis for head and neck squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115(3):385–92. doi:10.​1016/​j.​oooo.​2012.​12.​013.CrossRefPubMed
15.
Zurück zum Zitat Chen HC, Jeng YM, Yuan RH, Hsu HC, Chen YL. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis. Ann Surg Oncol. 2012;19(6):2011–9. doi:10.1245/s10434-011-2159-4.CrossRefPubMed Chen HC, Jeng YM, Yuan RH, Hsu HC, Chen YL. SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis. Ann Surg Oncol. 2012;19(6):2011–9. doi:10.​1245/​s10434-011-2159-4.CrossRefPubMed
16.
Zurück zum Zitat Noguchi A, Kikuchi K, Zheng H, Takahashi H, Miyagi Y, Aoki I, et al. SIRT1 expression is associated with a poor prognosis, whereas DBC1 is associated with favorable outcomes in gastric cancer. Cancer Med. 2014;3(6):1553–61. doi:10.1002/cam4.310.CrossRefPubMedPubMedCentral Noguchi A, Kikuchi K, Zheng H, Takahashi H, Miyagi Y, Aoki I, et al. SIRT1 expression is associated with a poor prognosis, whereas DBC1 is associated with favorable outcomes in gastric cancer. Cancer Med. 2014;3(6):1553–61. doi:10.​1002/​cam4.​310.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Kikuchi K, Noguchi A, Takahashi H, Zheng H, Kameda Y, Sekiguchi H, et al. High SIRT1 expression and low DBC1 expression are associated with poor prognosis in colorectal cancer. J Cancer Therapeut Res. 2013;2:1–8. doi:10.7243/2050-120X-2-1.CrossRef Kikuchi K, Noguchi A, Takahashi H, Zheng H, Kameda Y, Sekiguchi H, et al. High SIRT1 expression and low DBC1 expression are associated with poor prognosis in colorectal cancer. J Cancer Therapeut Res. 2013;2:1–8. doi:10.​7243/​2050-120X-2-1.CrossRef
28.
Zurück zum Zitat Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Luscher B, et al. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc Natl Acad Sci U S A. 2012;109(4):E187–196. doi:10.1073/pnas.1105304109.CrossRefPubMed Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Luscher B, et al. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc Natl Acad Sci U S A. 2012;109(4):E187–196. doi:10.​1073/​pnas.​1105304109.CrossRefPubMed
33.
Zurück zum Zitat Mulder KW, Wang X, Escriu C, Ito Y, Schwarz RF, Gillis J, et al. Diverse epigenetic strategies interact to control epidermal differentiation. Nat Cell Biol. 2012;14(7):753–63. doi:10.1038/ncb2520.CrossRefPubMed Mulder KW, Wang X, Escriu C, Ito Y, Schwarz RF, Gillis J, et al. Diverse epigenetic strategies interact to control epidermal differentiation. Nat Cell Biol. 2012;14(7):753–63. doi:10.​1038/​ncb2520.CrossRefPubMed
37.
Zurück zum Zitat Chiou S, Yu C, Huang C, Lin S, Liu S, Tsai T, et al. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 2013;14:4085–95. doi.CrossRef Chiou S, Yu C, Huang C, Lin S, Liu S, Tsai T, et al. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res. 2013;14:4085–95. doi.CrossRef
40.
Zurück zum Zitat Yoshikawa M, Tsuchihashi K, Ishimoto T, Yae T, Motohara T, Sugihara E, et al. xCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma. Cancer Res. 2013;73(6):1855–66. doi:10.1158/0008-5472.CAN-12-3609-T.CrossRefPubMed Yoshikawa M, Tsuchihashi K, Ishimoto T, Yae T, Motohara T, Sugihara E, et al. xCT inhibition depletes CD44v-expressing tumor cells that are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma. Cancer Res. 2013;73(6):1855–66. doi:10.​1158/​0008-5472.​CAN-12-3609-T.CrossRefPubMed
41.
Zurück zum Zitat Kikuchi K, Tsutsumi K, Ohta Y, Yasumoto S. Time correlation of commitment to calcium-induced apoptosis and terminal differentiation in human ectocervical keratinocytes in suspension cultures. Cell Growth Differ. 1997;8(5):571–9.PubMed Kikuchi K, Tsutsumi K, Ohta Y, Yasumoto S. Time correlation of commitment to calcium-induced apoptosis and terminal differentiation in human ectocervical keratinocytes in suspension cultures. Cell Growth Differ. 1997;8(5):571–9.PubMed
42.
Zurück zum Zitat Matsubara R, Kawano S, Kiyosue T, Goto Y, Hirano M, Jinno T, et al. Increased DeltaNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma. Int J Oncol. 2011;39(6):1391–9. doi:10.3892/ijo.2011.1151.PubMed Matsubara R, Kawano S, Kiyosue T, Goto Y, Hirano M, Jinno T, et al. Increased DeltaNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma. Int J Oncol. 2011;39(6):1391–9. doi:10.​3892/​ijo.​2011.​1151.PubMed
44.
Zurück zum Zitat Chakrabarti R, Wei Y, Hwang J, Hang X, Andres Blanco M, Choudhury A, et al. DeltaNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. Nat Cell Biol. 2014;16(10):1004–15. doi:10.1038/ncb3040.CrossRefPubMedPubMedCentral Chakrabarti R, Wei Y, Hwang J, Hang X, Andres Blanco M, Choudhury A, et al. DeltaNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling. Nat Cell Biol. 2014;16(10):1004–15. doi:10.​1038/​ncb3040.CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Sommer M, Poliak N, Upadhyay S, Ratovitski E, Nelkin BD, Donehower LA, et al. DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle. 2006;5(17):2005–11. doi.CrossRefPubMed Sommer M, Poliak N, Upadhyay S, Ratovitski E, Nelkin BD, Donehower LA, et al. DeltaNp63alpha overexpression induces downregulation of Sirt1 and an accelerated aging phenotype in the mouse. Cell Cycle. 2006;5(17):2005–11. doi.CrossRefPubMed
48.
Zurück zum Zitat Mattiske S, Ho K, Noll JE, Neilsen PM, Callen DF, Suetani RJ. TAp63 regulates oncogenic miR-155 to mediate migration and tumour growth. Oncotarget. 2013;4(11):1894–903. doi.CrossRefPubMedPubMedCentral Mattiske S, Ho K, Noll JE, Neilsen PM, Callen DF, Suetani RJ. TAp63 regulates oncogenic miR-155 to mediate migration and tumour growth. Oncotarget. 2013;4(11):1894–903. doi.CrossRefPubMedPubMedCentral
49.
Metadaten
Titel
Association of SIRT1 and tumor suppressor gene TAp63 expression in head and neck squamous cell carcinoma
verfasst von
Keiji Kikuchi
Akira Noguchi
Rika Kasajima
Yohei Miyagi
Daisuke Hoshino
Naohiko Koshikawa
Akira Kubota
Tomoyuki Yokose
Yasuo Takano
Publikationsdatum
01.10.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 10/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3515-y

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