Regulation and function of Myb-binding protein 1A (MYBBP1A) in cellular senescence and pathogenesis of head and neck cancer

• Verfasst von: George, Babitha [VerfasserIn]
• Verfasst von: Horn, Dominik [VerfasserIn]
• Verfasst von: Bayo, Pilar [VerfasserIn]
• Verfasst von: Plath, Karim [VerfasserIn]
• Verfasst von: Flechtenmacher, Christa [VerfasserIn]
• Verfasst von: Grabe, Niels [VerfasserIn]
• Verfasst von: Plinkert, Peter K. [VerfasserIn]
• Verfasst von: Heß, Jochen [VerfasserIn]
• Titel: Regulation and function of Myb-binding protein 1A (MYBBP1A) in cellular senescence and pathogenesis of head and neck cancer
• Verf.angabe: Babitha George, Dominik Horn, Pilar Bayo, Karim Zaoui, Christa Flechtenmacher, Niels Grabe, Peter Plinkert, Valery Krizhanovsky, Jochen Hess
• E-Jahr: 2015
• Jahr: 17 December 2014
• Umfang: 9 S.
• Fussnoten: Gesehen am 16.08.2017
• Titel Quelle: Enthalten in: Cancer letters
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1975
• Jahr Quelle: 2015
• Band/Heft Quelle: 358(2015), 2, Seite 191-199
• ISSN Quelle: 1872-7980
• DOI: doi:10.1016/j.canlet.2014.12.042
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cancer
• Sach-SW: DNA damage
• Sach-SW: Stress response
• Sach-SW: Treatment failure
• K10plus-PPN: 1562464590

Abstract

Myb-binding protein 1A (MYBBP1A) is a nucleolar protein implicated in stress response and carcinogenesis; however, its functional contribution to senescence remains elusive. In this study we show decreased MYBBP1A protein levels in tumor cells after treatment with etoposide, a potent inducer of DNA damage. Although silencing of MYBBP1A expression was not sufficient to induce senescence, it significantly increased the relative abundance of senescent cells after DNA damage. We found an inverse regulation of MYBBP1A and AKT phosphorylation (pAKT(Ser473)), which was characteristic for the pre-senescent state after etoposide administration in vitro. Tissue microarrays with tumor specimens from primary oropharyngeal squamous cell carcinoma (OPSCC) patients (n = 61) by immunohistochemistry revealed a significant correlation between MYBBP1AlowpAKT(Ser473)high staining pattern and shorter progression-free (p = 0.007) or overall survival (p < 0.001). Multivariate analysis showed that MYBBP1AlowpAKT(Ser473)high staining pattern is an independent prognosticator for OPSCC. Taken together, our study points to a critical role of MYBBP1A in the regulation of senescence under genotoxic stress and that a MYBBP1AlowAKT(Ser473)high staining pattern serves not only as a marker for the pre-senescent stage but also as an indicator of OPSCC patients at high risk for treatment failure.