SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/β-catenin signaling pathway.

Dandan Chen, Shang Gao, Fei Gao, Ai Liu, Jiangxia Li, Jisheng Li, Qiji Liu

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2023 Apr

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SMEK1, also known as PP4R3α, the regulatory subunit 3α of serine and threonine phosphatase PP4, participates in diversely critical biological processes such as the integration of centromere, deacetylation of histones, asymmetric divisions of neuroblast, and other crucial cellular activities. SMEK1 was formerly reported to play a part in carcinogenesis. This study aims to reveal the role of SMEK1 in lung adenocarcinoma and the underlying molecular mechanism. Using immunohistochemical (IHC) staining, the protein level of SMEK1 in lung adenocarcinoma and adjacent non-tumor tissue was detected. The functional role of SMEK1 in cell proliferation and invasion was explored using cell counting kit-8 and Transwell assay, respectively. Xenograft tumor experiment was used to investigate the effect of SMEK1 on tumor growth in vivo. The alteration of Wnt/β-catenin signaling pathway was detected by Western blotting, quantitative PCR, and dual-luciferase reporter assays. SMEK1 was highly expressed at the protein level in lung adenocarcinoma compared to the adjacent non-tumor tissue. In vitro, suppression of SMEK1 significantly decreased the proliferation, migration, and invasion of lung adenocarcinoma cell lines, while overexpression of SMEK1 enhanced above abilities. The xenograft model demonstrated that down-regulation of SMEK1 significantly inhibited tumor growth in vivo. In addition, we found that SMEK1 could positively regulate Wnt/β-catenin signaling in lung adenocarcinoma cell lines. SMEK1 exerts a cancer-promoting effect in lung adenocarcinoma by activating Wnt/β-catenin signaling. © 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).

Citation

Dandan Chen, Shang Gao, Fei Gao, Ai Liu, Jiangxia Li, Jisheng Li, Qiji Liu. SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/β-catenin signaling pathway. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2023 Apr;25(4):976-986