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

被引:131
作者
Han, Yu [1 ,2 ,3 ,4 ]
Liu, Chao [5 ,6 ]
Zhang, Dongfang [1 ,2 ,3 ,4 ]
Men, Hongchao [1 ,2 ,3 ,4 ]
Huo, Lifang [2 ,3 ,7 ]
Geng, Qiaowei [1 ,2 ,3 ,4 ]
Wang, Shengnan [1 ,2 ,3 ,4 ]
Gao, Yiting [1 ,2 ,3 ,4 ]
Zhang, Wei [2 ,3 ,7 ]
Zhang, Yongjian [1 ,2 ,3 ,4 ]
Jia, Zhanfeng [1 ,2 ,3 ,4 ]
机构
[1] Hebei Med Univ, Dept Pharmacol, 361 Zhongshan East Rd, Shijiazhuang 050017, Hebei, Peoples R China
[2] Hebei Med Univ, Inst Med Sci & Hlth, Ctr Innovat Drug Res & Evaluat, Shijiazhuang 050017, Hebei, Peoples R China
[3] Hebei Med Univ, Minist Educ, Key Lab Neural & Vasc Biol, Shijiazhuang 050017, Hebei, Peoples R China
[4] Hebei Med Univ, Key Lab New Drug Pharmacol & Toxicol, Shijiazhuang 050017, Hebei, Peoples R China
[5] Hebei Med Univ, Dept Lab Anim Sci, Shijiazhuang 050017, Hebei, Peoples R China
[6] Hebei Med Univ, Hebei Key Lab Hebei Lab Anim Sci, Shijiazhuang 050017, Hebei, Peoples R China
[7] Hebei Med Univ, Inst Chinese Integrat Med, Dept Pharmacol, Shijiazhuang 050017, Hebei, Peoples R China
基金
中国国家自然科学基金;
关键词
Piezo type mechanosensitive ion channel component 1; prostate cancer; Ca2+ signal; Akt; mTOR pathway; cell cycle; HUMAN GLIOBLASTOMA; GENE-EXPRESSION; STRETCH; PROTEIN; GROWTH; APOPTOSIS; PRESSURE; SURVIVAL; CA2+; TOUCH;
D O I
10.3892/ijo.2019.4839
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 G(0)/G(1) 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 G(0)/G(1) 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.
引用
收藏
页码:629 / 644
页数:16
相关论文
共 51 条
[1]   Modulation of the Ras/Raf/MEK/ERK pathway by Ca2+, and calmodulin [J].
Agell, N ;
Bachs, O ;
Rocamora, N ;
Villalonga, P .
CELLULAR SIGNALLING, 2002, 14 (08) :649-654
[2]   The Mechanosensitive Ion Channel Piezo1 Is Inhibited by the Peptide GsMTx4 [J].
Bae, Chilman ;
Sachs, Frederick ;
Gottlieb, Philip A. .
BIOCHEMISTRY, 2011, 50 (29) :6295-6300
[3]   Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer [J].
Booy, E. P. ;
Henson, E. S. ;
Gibson, S. B. .
ONCOGENE, 2011, 30 (20) :2367-2378
[4]   Human prostate cancer risk factors [J].
Bostwick, DG ;
Burke, HB ;
Djakiew, D ;
Euling, S ;
Ho, SM ;
Landolph, J ;
Morrison, H ;
Sonawane, B ;
Shifflett, T ;
Waters, DJ ;
Timms, B .
CANCER, 2004, 101 (10) :2371-2490
[5]   A tense situation: forcing tumour progression [J].
Butcher, Darci T. ;
Alliston, Tamara ;
Weaver, Valerie M. .
NATURE REVIEWS CANCER, 2009, 9 (02) :108-122
[6]   UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses [J].
Chandrashekar, Darshan S. ;
Bashel, Bhuwan ;
Balasubramanya, Sai Akshaya Hodigere ;
Creighton, Chad J. ;
Ponce-Rodriguez, Israel ;
Chakravarthi, Balabhadrapatruni V. S. K. ;
Varambally, Sooryanarayana .
NEOPLASIA, 2017, 19 (08) :649-658
[7]   A Feedforward Mechanism Mediated by Mechanosensitive Ion Channel PIEZO1 and Tissue Mechanics Promotes Glioma Aggression [J].
Chen, Xin ;
Wanggou, Siyi ;
Bodalia, Ankur ;
Zhu, Min ;
Dong, Weifan ;
Fan, Jerry J. ;
Yin, Wen Chi ;
Min, Hyun-Kee ;
Hu, Malini ;
Draghici, Diana ;
Dou, Wenkun ;
Li, Feng ;
Coutinho, Fiona J. ;
Whetstone, Heather ;
Kushida, Michelle M. ;
Dirks, Peter B. ;
Song, Yuanquan ;
Hui, Chi-Chung ;
Sun, Yu ;
Wang, Lu-Yang ;
Li, Xuejun ;
Huang, Xi .
NEURON, 2018, 100 (04) :799-+
[8]   Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels [J].
Coste, Bertrand ;
Mathur, Jayanti ;
Schmidt, Manuela ;
Earley, Taryn J. ;
Ranade, Sanjeev ;
Petrus, Matt J. ;
Dubin, Adrienne E. ;
Patapoutian, Ardem .
SCIENCE, 2010, 330 (6000) :55-60
[9]   Pathological and molecular aspects of prostate cancer [J].
DeMarzo, AM ;
Nelson, WG ;
Isaacs, WB ;
Epstein, JI .
LANCET, 2003, 361 (9361) :955-964
[10]   Glycogen synthase kinase 3β regulates cyclin D1 proteolysis and subcellular localization [J].
Diehl, JA ;
Cheng, MG ;
Roussel, MF ;
Sherr, CJ .
GENES & DEVELOPMENT, 1998, 12 (22) :3499-3511