TRPC5 expression promotes the proliferation and invasion of papillary thyroid carcinoma through the HIF-1α/Twist pathway

Jing Yang; Yue Cheng; Yan Nie; Bole Tian; Jing Huang; Rixiang Gong; Zhihui Li; Jingqiang Zhu; Yanping Gong

doi:10.1016/j.tranon.2023.101809

TRPC5 expression promotes the proliferation and invasion of papillary thyroid carcinoma through the HIF-1α/Twist pathway

Transl Oncol. 2024 Jan:39:101809. doi: 10.1016/j.tranon.2023.101809. Epub 2023 Oct 31.

Authors

Jing Yang¹, Yue Cheng², Yan Nie³, Bole Tian⁴, Jing Huang¹, Rixiang Gong¹, Zhihui Li¹, Jingqiang Zhu¹, Yanping Gong⁵

Affiliations

¹ Department of Thyroid Surgery, West China Hospital, Sichuan University, China; Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
² Department of Otorhinolaryngology-Head and Neck Surgery, Sichuan Electric Power Hospital, China.
³ West China School of Medicine, Sichuan University, China.
⁴ Department of pancreatic Surgery, West China Hospital, Sichuan University, China.
⁵ Department of Thyroid Surgery, West China Hospital, Sichuan University, China; Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: gongyanping@wchscu.cn.

Abstract

Objective: This study aimed to investigate the effect of TRPC5 on PTC (papillary thyroid carcinoma) proliferation and invasion.

Methods: Immunofluorescence and western blot were used to evaluate the expression of TRPC5 in paraffin sections and clinical tissues. Overexpression and silencing of TRPC5 to generate the cells for in vitro experiments. Wound-healing assay, transwell invasion assay, MTT assay, and in vivo tumorigenicity assay were used to determine cell proliferation and cell migration in vitro and in vivo. Real-time PCR was used to test the expression of TRPC5. Western blot was used to test the expression of downstream factors: E-cadherin, Vimentin, MMP-9, MMP-2, TRPC5, ZEB, Snail, and Twist.

Results: The level of TRPC5 protein expression was higher in PTC than in adjacent normal thyroid tissue. TPC-1 cells overexpressing TRPC5 were more proliferative, had longer migration distances, and increased the number of invading cells. TPC-1 cells silenced with TRPC5 had a weaker proliferation capacity, shorter migration distances, and a reduced number of invading cells. Overexpression and silencing of TRPC5 modulated E-cadherin, Vimentin, MMP-9, MMP-2, TRPC5, and Twist, but did not affect ZEB and Snail. The results of tumor formation experiments in nude mice showed that inhibition of TRPC5 expression suppressed the volume and weight of transplanted tumors.

Conclusion: TRPC5 induced papillary thyroid cancer metastasis and progression via up-regulated HIF-1α signaling in vivo and in vitro. High TRPC5 expression is a biomarker for lymph node metastasis at its early stages.

Keywords: Invasion; Papillary thyroid carcinoma; Proliferation; TRPC5.