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机械敏感性离子通道 Piezo1 通过激活 Akt/mTOR 通路和加速细胞周期促进前列腺癌的发展。

Mechanosensitive ion channel Piezo1 promotes prostate cancer development through the activation of the Akt/mTOR pathway and acceleration of cell cycle.

机构信息

Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.

Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.

出版信息

Int J Oncol. 2019 Sep;55(3):629-644. doi: 10.3892/ijo.2019.4839. Epub 2019 Jul 15.

Abstract

Prostate cancer is one of the most common types of cancer affecting men worldwide; however, its etiology and pathological mechanisms remain poorly understood. Mechanical stimulation plays a key role in prostate cancer development. Piezo type mechanosensitive ion channel component 1 (Piezo1), which functions as a cell sensor and transducer of mechanical stimuli, may have a crucial role in the development of prostate cancer. In the present study, the expression of the Piezo1 channel was demonstrated to be significantly elevated in prostate cancer cell lines and in human prostate malignant tumor tissues. Downregulation of Piezo1 significantly suppressed the viability, proliferation and migration of prostate cancer cells in vitro, and inhibited prostate tumor growth in vivo. The activation of the Akt/mTOR pathway or acceleration of cell cycle progression from G0/G1 to S phase may downstream consequences of Piezo 1 signal pathway activation. Downregulation of Piezo1 considerably suppressed Ca2+ signal increments, inhibited the phosphorylation of Akt and mTOR and arrested the cell cycle of prostate cancer cells at G0/G1 phase in while inhibiting the activation of CDK4 and cyclin D1. Taken together, these findings suggest that Piezo1 channels have a crucial role in prostate cancer development and may, therefore, be a novel therapeutic target in the treatment of prostate cancer.

摘要

前列腺癌是全球男性最常见的癌症类型之一,但它的病因和病理机制仍不清楚。机械刺激在前列腺癌的发展中起着关键作用。Piezo 型机械敏感离子通道成分 1(Piezo1)作为细胞对机械刺激的传感器和转换器,可能在前列腺癌的发展中起关键作用。在本研究中,发现 Piezo1 通道在前列腺癌细胞系和人前列腺恶性肿瘤组织中的表达显著升高。Piezo1 的下调显著抑制了前列腺癌细胞在体外的活力、增殖和迁移,并抑制了体内前列腺肿瘤的生长。Akt/mTOR 通路的激活或细胞周期从 G0/G1 期向 S 期的加速可能是 Piezo1 信号通路激活的下游后果。Piezo1 的下调显著抑制了 Ca2+信号的增加,抑制了 Akt 和 mTOR 的磷酸化,并将前列腺癌细胞的细胞周期阻滞在 G0/G1 期,同时抑制了 CDK4 和 cyclin D1 的激活。综上所述,这些发现表明 Piezo1 通道在前列腺癌的发展中起着至关重要的作用,因此可能成为治疗前列腺癌的新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/296a/6685593/e991d34509b4/IJO-55-03-0629-g00.jpg

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