Expression and functionality of TRPV1 in breast cancer cells

IF 3.3 4区 医学 Q2 ONCOLOGY
L. Weber, Klaudia Al-Refae, Gerhard Wölk, G. Bonatz, J. Altmüller, C. Becker, G. Gisselmann, H. Hatt
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引用次数: 71

Abstract

Transient receptor potential (TRP) channels contribute to the regulation of intracellular calcium, which can promote cancer hallmarks in cases of dysregulation of gene transcription and calcium-dependent pro-proliferative or anti-apoptotic mechanisms. Several studies have begun to elucidate the roles of TRPV1, TRPV6, TRPM8, and TRPC1 in cancer progression; however, no study has examined the expression profiles of human TRP channels in breast cancer on a large scale. This study focused on the expression and functionality of TRPV1, a nonselective cation channel that was found to be expressed in different carcinoma tissues. Next-generation sequencing analyses revealed the expression of TRPV1 in several native breast cancer tissues, which was subsequently validated via reverse transcriptase-polymerase chain reaction. Activation of TRPV1 by its ligand capsaicin was associated with the growth inhibition of some cancer cell types; however, the signaling components involved are complex. In this study, stimulation by the TRPV1 agonist, capsaicin, of SUM149PT cells, a model system for the most aggressive breast cancer subtype, triple-negative breast cancer, led to intracellular calcium signals that were diminished by the specific TRPV1 antagonist, capsazepin. Activation of TRPV1 by capsaicin caused significant inhibition of cancer cell growth and induced apoptosis and necrosis. In conclusion, the current study revealed the expression profiles of human TRP channels in 60 different breast cancer tissues and cell lines and furthermore validated the antitumor activity of TRPV1 against SUM149PT breast cancer cells, indicating that activation of TRPV1 could be used as a therapeutic target, even in the most aggressive breast cancer types.
TRPV1在乳腺癌细胞中的表达和功能
瞬时受体电位(TRP)通道有助于调节细胞内钙,在基因转录和钙依赖性促增殖或抗凋亡机制失调的情况下,可以促进癌症标志。一些研究已经开始阐明TRPV1、TRPV6、TRPM8和TRPC1在癌症进展中的作用;然而,目前还没有研究大规模检测人类TRP通道在乳腺癌中的表达谱。本研究的重点是TRPV1的表达和功能,TRPV1是一种非选择性阳离子通道,被发现在不同的癌组织中表达。新一代测序分析揭示了TRPV1在几种天然乳腺癌组织中的表达,随后通过逆转录-聚合酶链反应验证了这一点。TRPV1被其配体辣椒素激活与某些类型癌细胞的生长抑制有关;然而,所涉及的信令组件是复杂的。在这项研究中,TRPV1激动剂辣椒素刺激SUM149PT细胞(最具侵袭性的乳腺癌亚型,三阴性乳腺癌的模型系统),导致细胞内钙信号被特异性TRPV1拮抗剂辣椒素减少。辣椒素激活TRPV1可显著抑制癌细胞生长,诱导细胞凋亡和坏死。总之,本研究揭示了人类TRP通道在60种不同乳腺癌组织和细胞系中的表达谱,进一步验证了TRPV1对SUM149PT乳腺癌细胞的抗肿瘤活性,表明激活TRPV1可以作为治疗靶点,即使在最具侵袭性的乳腺癌类型中也是如此。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
40
审稿时长
16 weeks
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