SGSM2 inhibits thyroid cancer progression by activating RAP1 and enhancing competitive RAS inhibition

Su, Xi1; Chen, Dong1; Zhu, Lizhang1; Jia, Hao1; Cai, Jiaxuan2,3; Li, Peng1; Han, Bin1; Wang, Donglai1; Li, Hongtao4; Fan, Jiaqian5; Gu, Mengwei6; Zhou, Yaqi7; Guan, Haixia8; Wei, Wei1

2022-03-09

10.1038/s41419-022-04598-y

Cell Death & Disease   影响因子和分区

2041-4889

Thyroid cancer (TC) is one of the most common malignancies involving the head and neck, and its incidences are increasing every year. Small G protein signaling modulators 2 (SGSM2) belongs to a newly identified protein group that contributes to numerous cancer progression. However, its role in TC remains unknown. The aim of this study was to explore the functions and underlying molecular mechanism of SGSM2 in the progression of thyroid tumorigenesis. Here, we demonstrated that SGSM2 expression was markedly decreased in TC, and that lower SGSM2 expression was potentially related to worse patient prognosis. Meanwhile, the SGSM2 levels were not directly correlated with BRAF or RAS mutations in TC. Based on our functional analysis, ectopic SGSM2 expression strongly prevented cell proliferation, migration, invasion, and tumorigenic activity in TC cells that harbored wild type RAS. Mechanistically, we demonstrated that SGSM2 interacted with Small G protein Ras-associated protein 1(RAP1) and augmented its activity. Activated RAP1 then competitively suppressed RAS activation and thereby downregulated output of MAPK/ERK and PI3K/Akt networks, which are primary contributors of TC. In summary, the present study reports a tumor suppressive role of SGSM2 in TC. Moreover, we revealed the underlying molecular mechanism, thus providing a potential therapeutic target for TCs that harbor wild type RAS.

SCI

英语

其他

National Natural Science Foundation of China[82103130,82002885] ; Shenzhen Science and Technology Program[JCYJ20210324110402006] ; China Postdoctoral Science Foundation[2021M692159] ; Shenzhen Key Medical Discipline Construction Fund[SZXK017] ; Shenzhen San-Ming Project[SZSM201612010]

Cell Biology

Cell Biology

WOS:000766589400001

SPRINGERNATURE

Web of Science

1.Peking Univ Shenzhen Hosp, Shenzhen Peking Univ Hong Kong Univ Sci & Technol, Dept Thyroid & Parathyroid Surg, Shenzhen, Guangdong, Peoples R China
2.Chinese Acad Sci, Ctr Energy Metab & Reprod, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China
3.Univ Chinese Acad Sci, Shenzhen Coll Adv Technol, Shenzhen, Peoples R China
4.Southern Univ Sci & Technol, Dept Stat & Data Sci, Shenzhen, Peoples R China
5.Chinese Univ Hong Kong, Sch Life & Hlth Sci, Shenzhen, Guangdong, Peoples R China
6.Beijing Century Joyo Informat Technol Co Ltd, Shenzhen, Peoples R China
7.Peking Univ Shenzhen Hosp, ShenZhen Peking Univ Hong Kong Univ Sci & Technol, Dept Otorhinolaryngol, Shenzhen, Peoples R China
8.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Dept Endocrinol, Guangzhou, Guangdong, Peoples R China

Su, Xi,Chen, Dong,Zhu, Lizhang,et al. SGSM2 inhibits thyroid cancer progression by activating RAP1 and enhancing competitive RAS inhibition[J]. Cell Death & Disease,2022,13(3).

Su, Xi.,Chen, Dong.,Zhu, Lizhang.,Jia, Hao.,Cai, Jiaxuan.,...&Wei, Wei.(2022).SGSM2 inhibits thyroid cancer progression by activating RAP1 and enhancing competitive RAS inhibition.Cell Death & Disease,13(3).

Su, Xi,et al."SGSM2 inhibits thyroid cancer progression by activating RAP1 and enhancing competitive RAS inhibition".Cell Death & Disease 13.3(2022).