Downregulation of ARMC8 promotes tumorigenesis through activating Wnt/β-catenin pathway and EMT in cutaneous squamous cell carcinomas

被引:13
作者
Li, Xiangzhi [1 ,2 ]
Zhang, Chen [1 ]
Yuan, Yawen [1 ]
Wang, Yimeng [1 ]
Lu, Sheng [3 ]
Zhou, Zhaoming [1 ]
Zhen, Peilin [4 ]
Zhou, Meijuan [1 ]
机构
[1] Southern Med Univ, Sch Publ Hlth, Dept Radiat Med, Guangdong Prov Key Lab Trop Dis Res, 1023 Shatai South Rd, Guangzhou 510515, Peoples R China
[2] Guangxi Univ Sci & Technol, Affiliated Hosp 1, Dept Pathol, Liuzhou, Peoples R China
[3] Southern Med Univ, Sch Clin Med 1, Guangzhou, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Jiangmen Hosp, Jiangmen Cent Hosp, Jiangmen, Peoples R China
基金
中国国家自然科学基金;
关键词
ARMC8; Tumorigenesis; Wnt/beta-catenin; EMT; Cutaneous squamous cell carcinomas; EPITHELIAL-MESENCHYMAL TRANSITION; ARMADILLO-REPEAT PROTEINS; EXPRESSION; ARMC8-ALPHA; PROGRESSION; METASTASIS; INVASION; TWIST; RISK;
D O I
10.1016/j.jdermsci.2021.05.002
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background: Aberrant expression of Armadillo repeat containing 8 (ARMC8) plays crucial roles in tumor growth and metastasis of various cancers. The specific role of ARMC8 in cutaneous squamous cell carcinoma (cSCC) is yet to be elucidated. Objective: The present study aimed to investigate the molecular mechanisms of ARMC8 and epithelial-mesenchymal transition (EMT) in cSCC development and provide translational insights for future therapeutics. Methods: cSCC tumor specimens were used to determine the ARMC8 by immunohistochemistry. Three cSCC cell lines including HSC-1, HSC-5 and A431 as well as BALB/C mouse tumor model was utilized to study the potential mechanisms in tumorigenesis. Results: Our data identified ARMC8 as a direct downstream target of miR-664. We found that ARMC8 was remarkably low expression in cSCC patient specimens and cSCC cell lines. Knockdown of ARMC8 promotes tumorigenic behaviors such as increased cell proliferation, migration and invasion capacities in vitro and enhanced tumorigenicity in xenograft mouse model. Whereas ARMC8 over-expression inhibits tumorigenesis in cSCC. Together, it revealed ARMC8 functions as a tumor suppressor via restraining Wnt/beta-catenin pathway and epithelial-mesenchymal transition in cSCC. Conclusion: Our data verifies that aberrant expression of ARMC8 plays a vital role in carcinogenesis of cSCC. And overexpression of ARMC8 will facilitate future development of cSCC therapeutic interventions. (C) 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:184 / 192
页数:9
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