ARMC8 的下调通过激活 Wnt/β-catenin 通路和 EMT 促进皮肤鳞状细胞癌的发生。

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

机构信息

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China; Department of Pathology, The First Affiliated Hospital of Guangxi University of Science and Technology, Guangxi University of Science and Technology, Liuzhou, China.

Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

出版信息

J Dermatol Sci. 2021 Jun;102(3):184-192. doi: 10.1016/j.jdermsci.2021.05.002. Epub 2021 May 10.

DOI:10.1016/j.jdermsci.2021.05.002

PMID:34016486

Abstract

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/β-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.

摘要

背景

角蛋白重复含 8 （ARMC8）的异常表达在各种癌症的肿瘤生长和转移中起着关键作用。ARMC8 在皮肤鳞状细胞癌（cSCC）中的具体作用尚未阐明。

目的

本研究旨在探讨 ARMC8 在 cSCC 发展中的分子机制及其与上皮-间充质转化（EMT）的关系，为未来的治疗提供转化研究的思路。

方法

使用 cSCC 肿瘤标本通过免疫组织化学法来确定 ARMC8 的表达情况。使用三种 cSCC 细胞系（HSC-1、HSC-5 和 A431）以及 BALB/C 小鼠肿瘤模型来研究肿瘤发生中的潜在机制。

结果

我们的数据确定 ARMC8 是 miR-664 的直接下游靶标。我们发现 ARMC8 在 cSCC 患者标本和 cSCC 细胞系中表达明显下调。ARMC8 敲低可促进体外细胞增殖、迁移和侵袭能力增强以及异种移植小鼠模型中的肿瘤发生。而 ARMC8 的过表达可抑制 cSCC 的肿瘤发生。总之，ARMC8 通过抑制 Wnt/β-catenin 通路和 EMT 在 cSCC 中发挥肿瘤抑制作用。