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

TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the Transforming Growth Factor-β Signaling Pathway
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DOI:
10.1245/s10434-021-11132-5
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发表时间:
2021-12-02
影响因子:
3.7
通讯作者:
Otsuji, Eigo
Otsuji, Eigo
中科院分区:
医学2区
文献类型:
--
作者:
Kato, Shunji;Shiozaki, Atsushi;Otsuji, Eigo

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瞬时受体电位香草蛋白2 (TRPV2)是一个高度Ca2+渗透的离子通道,参与了许多细胞过程。它在各种人类癌症中表达;然而,TRPV2在胃癌(GC)中的作用仍然知之甚少。方法采用小干扰RNA (small-interfering RNA, siRNA)敲除GC细胞株中TRPV2基因的表达,研究TRPV2在GC细胞增殖、迁移和侵袭中的生物学作用。GC基因表达谱通过微阵列分析得到。免疫组化分析肿瘤组织切片中TRPV2的表达。结果敲低TRPV2可抑制胃癌细胞的迁移和侵袭能力。此外,微阵列分析显示,TRPV2与转化生长因子(TGF)- β信号通路相关。免疫组化染色显示,在GC患者中,TRPV2的强表达与淋巴浸润、静脉浸润、病理性T (pT)、病理性N (pN)及不良预后相关。结论TRPV2可能通过tgf - β信号通路促进肿瘤的迁移和侵袭,TRPV2的高表达与胃癌患者预后较差相关。
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)-beta 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-beta signaling pathway, and the strong expression of TRPV2 was associated with a worse prognosis in GC patients.