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PLCD1 Suppressed Cellular Proliferation, Invasion, and Migration via Inhibition of Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma

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Abstract

Background

Phospholipase C delta 1 (PLCD1) has been found to be abnormally expressed in various cancers. However, the potential roles of PLCD1 in esophageal squamous cell carcinoma (ESCC) are still unknown.

Methods

Western blot and qPCR were used to explore PLCD1 expression in various ESCC cells. MTT, colony formation assays, wound-healing assay, and transwell cell invasion assay were used to examine the cell viability in vitro. Western blot, qPCR, and luciferase assays were used to investigate the effects of PLCD1 on Wnt/β-catenin signaling pathway. The xenograft models in nude mice were established to explore the roles of PLCD1 in vivo.

Results

We found that the expression of PLCD1 in ESCC cells was significantly downregulated than that in normal esophageal epithelial cells. In addition, upregulation of PLCD1 decreased the capacity of TE-1 and EC18 cells in proliferation, invasion, and migration. Then, the expression of β-catenin/p-β-catenin, C-myc, cyclin D1, MMP9, and MMP7 was investigated. PLCD1 activity was found to be negatively associated with the expression of β-catenin, C-myc, cyclin D1, MMP9, and MMP7. Finally, the activity of PLCD1 in inhibiting ESCC proliferation in vivo was validated.

Conclusion

The inhibitory effects of PLCD1 on the proliferation, invasion, and migration of TE-1 and EC18 cells might be associated with inhibition of Wnt/β-catenin signaling pathway. PLCD1 played a key role in inhibiting ESCC carcinogenesis and progression in patients with ESCC.

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Funding

This study was funded by the National Natural Science Foundation of China (No. 81960438), Jiangxi Provincial Department of Education Project (Nos. 190792, 190790, 190842, and 190845), and a Grant from Natural Science Foundation of Guangdong Province (No. 2018A0303130233).

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Author notes

  1. Xin He and Fan Meng have contributed equally to this work.

Authors and Affiliations

  1. The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jangxi Province, China

    Xin He & Fan Meng

  2. Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, China

    Zhong-jian Yu, Xiong-jie Zhu, Ling-yu Qin, Xiao-ran Wu, Zhi-le Liu, Ying Li & Yan-fang Zheng

Authors
  1. Xin He
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  2. Fan Meng
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  3. Zhong-jian Yu
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  4. Xiong-jie Zhu
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  5. Ling-yu Qin
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  7. Zhi-le Liu
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  9. Yan-fang Zheng
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Contributions

XH, FM, and YFZ designed experiments. XH and FM carried out experiments. ZJY, LYQ, XRW, and ZLL performed bioinformatics analysis. ZLL, XJZ, and YL conducted statistical analysis. XH and YFZ wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yan-fang Zheng.

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Conflict of interest

The authors declared that they have no conflict of interest.

Ethics approval

All animal experiments were performed in accordance with the principles and procedures outlined in the Nanfang Medical University Guide for the Care and Use of Animals under the assurance number SCXK (Guangdong) 2008-0002. Approval was obtained from the Nanfang Hospital Animal Ethics Committee.

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He, X., Meng, F., Yu, Zj. et al. PLCD1 Suppressed Cellular Proliferation, Invasion, and Migration via Inhibition of Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma. Dig Dis Sci 66, 442–451 (2021). https://doi.org/10.1007/s10620-020-06218-1

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  • DOI: https://doi.org/10.1007/s10620-020-06218-1

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