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TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the Transforming Growth Factor-β Signaling Pathway

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Transient receptor potential vanilloid 2 (TRPV2) is a highly Ca2+-permeable ion channel that is involved in a number of cellular processes. It is expressed in various human cancers; however, the role of TRPV2 in gastric cancer (GC) remains poorly understood.

Methods

TRPV2 gene expression was knocked down in GC cell lines by small-interfering RNA (siRNA), and the biological roles of TRPV2 in the proliferation, migration, and invasion of GC cells were then investigated. The gene expression profile of GC was elucidated using a microarray analysis. TRPV2 expression in tumor tissue sections was analyzed by immunohistochemistry.

Results

The migration and invasion abilities of GC cells were inhibited by the knockdown of TRPV2. Moreover, the microarray assay revealed that TRPV2 was associated with the transforming growth factor (TGF)-β signaling pathway. Immunohistochemical staining showed that the strong expression of TRPV2 correlated with lymphatic invasion, venous invasion, pathological T (pT), pathological N (pN), and a poor prognosis in GC patients.

Conclusions

TRPV2 appeared to promote tumor migration and invasion via the TGF-β signaling pathway, and the strong expression of TRPV2 was associated with a worse prognosis in GC patients.

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Funding

This study was supported by Grants-in-Aid for Scientific Research (C) [18K08628, 18K08689, 19K09202,19K09182, 20K09016, and 20K09084] and a Grant-in-Aid for Young Scientists (19K18160) from the Japan Society for the Promotion of Science. The authors wish to thank Dr. Akifumi Matsumoto for advise on additional analysis for revision.

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Author notes

  1. Shunji Kato and Atsushi Shiozaki contributed equally to this work.

Authors and Affiliations

  1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Shunji Kato MD, Atsushi Shiozaki MD, PhD, Michihiro Kudou MD, PhD, Hiroki Shimizu MD, PhD, Toshiyuki Kosuga MD, PhD, Takuma Ohashi MD, PhD, Tomohiro Arita MD, PhD, Hirotaka Konishi MD, PhD, Shuhei Komatsu MD, PhD, Takeshi Kubota MD, PhD, Hitoshi Fujiwara MD, PhD, Kazuma Okamoto MD, PhD & Eigo Otsuji MD, PhD

  2. Department of Pathology, Kyoto City Hospital, Kyoto, Japan

    Mitsuo Kishimoto MD, PhD

  3. Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Eiichi Konishi MD, PhD

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  1. Shunji Kato MD
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Corresponding author

Correspondence to Atsushi Shiozaki MD, PhD.

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Disclosure

The authors declare that they have no conflicts of interest.

Ethical Approval

The Research Ethics Committee of the Kyoto Prefectural University of Medicine (No.ERB-C-1195) approved the protocols performed in the present study.

Informed Consent

All included patients provided comprehensive informed consent for the use of their clinical data and samples.

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Kato, S., Shiozaki, A., Kudou, M. et al. TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the Transforming Growth Factor-β Signaling Pathway. Ann Surg Oncol 29, 2944–2956 (2022). https://doi.org/10.1245/s10434-021-11132-5

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  • DOI: https://doi.org/10.1245/s10434-021-11132-5

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