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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

SMEK1 exerts a cancer-promoting effect in lung adenocarcinoma by activating Wnt/β-catenin signaling.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (81873878, 32070586, and 81671114) and Shandong Provincial Natural Science Foundation (ZR2020MH086, ZR2020LZL018).

Author information

Author notes

  1. Jisheng Li and Qiji Liu have contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, No. 44 West Wenhua Road, Jinan, 250012, Shandong, China

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

  2. Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wenhua Xi Road, Jinan, 250012, Shandong, China

    Jisheng Li

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  1. Dandan Chen
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  2. Shang Gao
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  4. Ai Liu
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  5. Jiangxia Li
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Contributions

QJL, JSL, and DDC designed the study. DDC performed the experiments, analyzed the data, and drafted the manuscript. JSL revised the manuscript and helped with English editing. SG, FG, and AL helped with experiments. QJL and JXL contributed essential reagents and tools. QJL and JSL supervised the data collection and the analysis of the data.

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Correspondence to Jisheng Li or Qiji Liu.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethic Committee of Shandong University.

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Chen, D., Gao, S., Gao, F. et al. SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/β-catenin signaling pathway. Clin Transl Oncol 25, 976–986 (2023). https://doi.org/10.1007/s12094-022-03001-8

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  • DOI: https://doi.org/10.1007/s12094-022-03001-8

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