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Downregulation of SLC9A8 Promotes Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer Cells via the IL6-JAK1/STAT3 Signaling Pathway

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Abstract

Background

SLC9A8 has been shown to be involved in mucus layer formation, intestinal mucosal integrity, and hyperproliferation of colitis-associated tumor development. However, its effects on the epithelial–mesenchymal transition (EMT) and the metastasis of colorectal cancer (CRC) remain unknown.

Aims

To explore whether SLC9A8 participates in EMT and the metastasis of CRC.

Methods

Western blotting and immunohistochemistry were performed to evaluate the expression of SLC9A8 in CRC patients. At the cellular level, the effect of SLC9A8 on proliferation, migration, and invasion was measured using cell viability analysis, flow cytometry analysis, and Transwell assays. Mouse tumor xenograft and metastasis models were established to analyze whether knockdown of SLC9A8 increased tumor volume, tumor weight, and metastasis. Moreover, whether downregulated expression of SLC9A8 promotes EMT via activation of the IL6-JAK1-STAT3 signaling pathway was investigated.

Results

SLC9A8 protein was downregulated in CRC tissues, and this downregulation was significantly associated with tumor size, lymph node status, pTNM stage, and poor prognosis. SLC9A8 overexpression markedly suppressed cell proliferation, migration, and invasion. Downregulation of SLC9A8 promoted CRC cell proliferation, migration, and invasion. Moreover, knockdown of SLC9A8 also increased tumor volume, tumor weight, and metastasis in vivo. Meanwhile, downregulation of SLC9A8 significantly promoted the in vitro migration of CRC cells via EMT by activating the IL6-JAK1/STAT3 signaling pathway.

Conclusions

Downregulation of SLC9A8 plays an important role in EMT and metastasis of CRC progression and may become a new potential therapeutic target for the treatment of CRC.

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Funding

The work was supported by the National Natural Science Foundation of China (82070544) and the Sichuan Science and Technology Program (2020YFS0239).

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Author notes

  1. Wei Liu and Chong Geng are co-first authors.

Authors and Affiliations

  1. Department of Gastroenterology, West China Hospital of Sichuan University, No.37 GuoXue Street, Chengdu, 610041, China

    Wei Liu, Xiao Li, Yanni Li, Shuailing Song & Chunhui Wang

  2. Laboratory of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China

    Chong Geng

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  1. Wei Liu
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Correspondence to Chunhui Wang.

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Liu, W., Geng, C., Li, X. et al. Downregulation of SLC9A8 Promotes Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer Cells via the IL6-JAK1/STAT3 Signaling Pathway. Dig Dis Sci 68, 1873–1884 (2023). https://doi.org/10.1007/s10620-022-07805-0

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