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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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Abstract
Cancer: A trio of proteins to tackle tumors New understanding of the interactions between three proteins sheds light on their role in either promoting or restricting the development of tumors called squamous cell carcinomas, which account for over 90% of all cancers in the head and neck. Researchers in South Korea led by Sang Yoon Kim and Seong Who Kim at the University of Ulsan, Seoul, investigated the role of the proteins Sirt6, Sirt1 and MDM2 in controlling the death of cancer cells caused by chemicals called reactive oxygen species (ROS). The effects of Sirt6 and Sirt1 combine to regulate ROS-induced cancer cell death. Sirt6 controls the activity of MDM2, stimulating ROS production. Sirt6 also influences MDM2 to suppress Sirt1 activity, thereby also promoting cancer cell death. Drugs affecting these three proteins could offer new approaches to anti-cancer therapy.

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.
Author(s)
김상윤김승후박정제원성준장효원Jeong Seok HwaJi Hyun SeoJong Sil LeeSo Young CheonSomi RyuYoung-Sool Hah
Issued Date
2021
Type
Article
Keyword
AgingApoptosisCancerCell deathHead and neck cancerHead and neck carcinomaHepatocellular carcinomaMDM2 proteinOral cancerProteinsReactive oxygen speciesSIRT1 proteinSquamous cell carcinomaTumorigenesisTumors생화학
DOI
10.1038/s12276-021-00578-y
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7821
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_nrf_kci_oai_kci_go_kr_ARTI_9763518&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,MDM2-dependent%20Sirt1%20degradation%20is%20a%20prerequisite%20for%20Sirt6-mediated%20cell%20death%20in%20head%20and%20neck%20cancers&offset=0&pcAvailability=true
Publisher
EXPERIMENTAL AND MOLECULAR MEDICINE
Location
미국
Language
영어
ISSN
1226-3613
Citation Volume
53
Citation Number
3
Citation Start Page
422
Citation End Page
431
Appears in Collections:
Medicine > Medicine
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