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PTEN Gene Induces Cell Invasion and Migration via Regulating AKT/GSK-3β/β-Catenin Signaling Pathway in Human Gastric Cancer

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Abstract

Background

Abnormality of PTEN gene and Wnt/β-catenin signaling have been strongly implicated in various malignant cancers. Recently, it has been noted that a functional interaction/cross-talk was found between the PTEN/PI3K/AKT and Wnt/β-catenin, which plays a key role in the development of cancers. However, few related studies on gastric cancer are available.

Aim

We examined the expression of PTEN and β-catenin in gastric cancer tissues and detected whether down-regulation of PTEN promotes the migration and invasion in gastric cancer cells along with its underlying mechanism.

Materials and Methods

Immunocytochemistry, a wound healing assay, a Matrigel invasion assay, an immunofluorescence staining were performed to detect expression of PTEN and β-catenin in gastric cancer and adjacent normal tissues, cell migration, cell invasion, and the effects of PTEN knockdown on β-catenin in cells, respectively. Further, MMP-2 and MMP-9 activities were analyzed by zymography assay. The changes in related proteins were further quantified by western blotting.

Results

Low expression of PTEN was found in majority of gastric cancer tissues, which showed significant associations with differentiation grade in gastric cancer patients. Further, a negative correlation was revealed between PTEN and β-catenin protein expression in gastric cancer tissues (r = − 0.546, P < 0.01). Additionally, PTEN knockdown promoted the migration and invasion of cells and caused an obvious increase in p-AKT, p-GSK-3β, β-catenin, E-cadherin, MMP-7, MMP-2, and MMP-9 in gastric cancer cells.

Conclusion

Our results indicated PTEN gene might induce cell invasion and migration via regulating AKT/GSK-3β/β-catenin signaling pathway, playing a vital role in the progression of gastric cancer.

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Acknowledgments

We are grateful to Mr. Hong Xia from the Key Laboratory of Hubei Province for Digestive System Disease for laboratory assistance, kindly guidance, help, advice, and support.

Funding

The study was supported by the research grants from the National Natural Science Foundation of China (Nos. 81372551 and 81572426).

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Authors and Affiliations

  1. Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhi-dong Road, Wuhan, 430060, Hubei Province, People’s Republic of China

    Jingjing Ma, Jixiang Zhang, Dandan Wu, Xue Hu, Jiao Li, Qingzhi Lan, Ya Liu & Weiguo Dong

  2. Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China

    Xufeng Guo

  3. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, People’s Republic of China

    Jingjing Ma, Xufeng Guo & Jixiang Zhang

  4. Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China

    Jingjing Ma & Jixiang Zhang

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  1. Jingjing Ma
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  2. Xufeng Guo
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Correspondence to Weiguo Dong.

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No potential conflict of interest relevant to this article was reported.

Ethical approval

All procedures performed in studies involving human participants were approved by Clinical Research Ethics Committee of Renmin Hospital of Wuhan University, which were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consents were obtained from all individual participants included in the study.

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Ma, J., Guo, X., Zhang, J. et al. PTEN Gene Induces Cell Invasion and Migration via Regulating AKT/GSK-3β/β-Catenin Signaling Pathway in Human Gastric Cancer. Dig Dis Sci 62, 3415–3425 (2017). https://doi.org/10.1007/s10620-017-4764-y

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  • DOI: https://doi.org/10.1007/s10620-017-4764-y

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