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KMID : 0620920210530030422
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Experimental & Molecular Medicine
2021 Volume.53 No. 3 p.422 ~ p.431
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MDM2-dependent Sirt1 degradation is a prerequisite for Sirt6-mediated cell death in head and neck cancers
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Park Jung-Je
Hah Young-Sool
Ryu So-Mi
Cheon So-Young
Won Seong-Jun
Lee Jong-Sil
Hwa Jeong-Seok
Seo Ji-Hyun
Chang Hyo-Won
Kim Seong-Who
Kim Sang-Yoon
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Abstract
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Sirt6 is involved in multiple biological processes, including aging, metabolism, and tumor suppression. Sirt1, another member of the sirtuin family, functionally overlaps with Sirt6, but its role in tumorigenesis is controversial. In this study, we focused on cell death in association with Sirt6/Sirt1 and reactive oxygen species (ROS) in head and neck squamous cell carcinomas (HNSCCs). Sirt6 induced cell death, as widely reported, but Sirt1 contributed to cell death only when it was suppressed by Sirt6 via regulation of MDM2. Sirt6 and Sirt6-mediated suppression of Sirt1 upregulated ROS, which further led to HNSCC cell death. These results provide insight into the molecular roles of Sirt6 and Sirt1 in tumorigenesis and could therefore contribute to the development of novel strategies to treat HNSCC.
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KEYWORD
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Oral cancer
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