Suppression of STIM1 inhibits the migration and invasion of human prostate cancer cells and is associated with PI3K/Akt signaling inactivation

Zhou,Yibin; Gu,Peng; Li,Jian; Li,Feng; Zhu,Jin; Gao,Peng; Zang,Yachen; Wang,Yongchang; Shan,Yuxi; Yang,Dongrong

doi:10.3892/or.2017.5961

Suppression of STIM1 inhibits the migration and invasion of human prostate cancer cells and is associated with PI3K/Akt signaling inactivation

Authors:
- Yibin Zhou
- Peng Gu
- Jian Li
- Feng Li
- Jin Zhu
- Peng Gao
- Yachen Zang
- Yongchang Wang
- Yuxi Shan
- Dongrong Yang
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Affiliations: Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China, Department of Urology, Xishan People's Hospital of Wuxi, Wuxi, Jiangsu 214000, P.R. China, Department of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/or.2017.5961
Pages: 2629-2636
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Store-operated calcium entry (SOCE) plays an important role in the invasion and migration of cancer cells. Stromal-interacting molecule 1 (STIM1) is a critical component in the SOCE. STIM1 has been attracting more and more attention due to its oncogenic potential. STIM1 inhibition suppresses cell proliferation, migration and invasion in a variety of cancer models both in vitro and in vivo. However, the role of STIM1 in prostate carcinogenesis, in particular, in tumor migration and invasion is unclear. Herein, we downregulated STIM1 in prostate cancer cells by lentivirus-mediated short hairpin (shRNA), and then studied its impacts on cell migration and invasion. We found that migration and invasion of prostate cancer cells were significantly inhibited after the suppression of STIM1. Furthermore, we demonstrated that the PI3K/Akt signaling pathway was inactivated by STIM1 knockdown. The PI3K inhibitor LY294002 synergized with STIM1 knockdown to inhibit cell motility. Our results revealed that STIM1 may act as a novel regulator to promote migration and invasion of prostate cancer cells and is associated with the activation of the PI3K/Akt signaling pathway.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Lucas JM, Heinlein C, Kim T, Hernandez SA, Malik MS, True LD, Morrissey C, Corey E, Montgomery B, Mostaghel E, et al: The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov. 4:1310–1325. 2014. View Article : Google Scholar : PubMed/NCBI
3	Shah ET, Upadhyaya A, Philp LK, Tang T, Skalamera D, Gunter J, Nelson CC, Williams ED and Hollier BG: Repositioning ‘old’ drugs for new causes: Identifying new inhibitors of prostate cancer cell migration and invasion. Clin Exp Metastasis. 33:385–399. 2016. View Article : Google Scholar : PubMed/NCBI
4	Abdullaev IF, Bisaillon JM, Potier M, Gonzalez JC, Motiani RK and Trebak M: Stim1 and Orai1 mediate CRAC currents and store-operated calcium entry important for endothelial cell proliferation. Circ Res. 103:1289–1299. 2008. View Article : Google Scholar : PubMed/NCBI
5	Berridge MJ, Lipp P and Bootman MD: The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 1:11–21. 2000. View Article : Google Scholar : PubMed/NCBI
6	Hu J, Qin K, Zhang Y, Gong J, Li N, Lv D, Xiang R and Tan X: Downregulation of transcription factor Oct4 induces an epithelial-to-mesenchymal transition via enhancement of Ca²⁺ influx in breast cancer cells. Biochem Biophys Res Commun. 411:786–791. 2011. View Article : Google Scholar : PubMed/NCBI
7	Lee KP, Yuan JP, Hong JH, So I, Worley PF and Muallem S: An endoplasmic reticulum/plasma membrane junction: STIM1/Orai1/TRPCs. FEBS Lett. 584:2022–2027. 2010. View Article : Google Scholar : PubMed/NCBI
8	Yang S, Zhang JJ and Huang XY: Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell. 15:124–134. 2009. View Article : Google Scholar : PubMed/NCBI
9	Chen YF, Chiu WT, Chen YT, Lin PY, Huang HJ, Chou CY, Chang HC, Tang MJ and Shen MR: Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci USA. 108:pp. 15225–15230. 2011; View Article : Google Scholar : PubMed/NCBI
10	Yang N, Tang Y, Wang F, Zhang H, Xu D, Shen Y, Sun S and Yang G: Blockade of store-operated Ca²⁺ entry inhibits hepatocarcinoma cell migration and invasion by regulating focal adhesion turnover. Cancer Lett. 330:163–169. 2013. View Article : Google Scholar : PubMed/NCBI
11	Li G, Zhang Z, Wang R, Ma W, Yang Y, Wei J and Wei Y: Suppression of STIM1 inhibits human glioblastoma cell proliferation and induces G0/G1 phase arrest. J Exp Clin Cancer Res. 32:202013. View Article : Google Scholar : PubMed/NCBI
12	King D, Yeomanson D and Bryant HE: PI3King the lock: Targeting the PI3K/Akt/mTOR pathway as a novel therapeutic strategy in neuroblastoma. J Pediatr Hematol Oncol. 37:245–251. 2015. View Article : Google Scholar : PubMed/NCBI
13	Chen X, Wang YW, Xing AY, Xiang S, Shi DB, Liu L, Li YX and Gao P: Suppression of SPIN1-mediated PI3K-Akt pathway by miR-489 increases chemosensitivity in breast cancer. J Pathol. 239:459–472. 2016. View Article : Google Scholar : PubMed/NCBI
14	Broek R Vander, Mohan S, Eytan DF, Chen Z and Van Waes C: The PI3K/Akt/mTOR axis in head and neck cancer: Functions, aberrations, cross-talk, and therapies. Oral Dis. 21:815–825. 2015. View Article : Google Scholar : PubMed/NCBI
15	Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS and Chung J: Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 15:1953–1962. 2001. View Article : Google Scholar : PubMed/NCBI
16	Yoeli-Lerner M, Yiu GK, Rabinovitz I, Erhardt P, Jauliac S and Toker A: Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT. Mol Cell. 20:539–550. 2005. View Article : Google Scholar : PubMed/NCBI
17	Tanno S, Tanno S, Mitsuuchi Y, Altomare DA, Xiao GH and Testa JR: AKT activation up-regulates insulin-like growth factor I receptor expression and promotes invasiveness of human pancreatic cancer cells. Cancer Res. 61:589–593. 2001.PubMed/NCBI
18	Mundi PS, Sachdev J, McCourt C and Kalinsky K: AKT in cancer: New molecular insights and advances in drug development. Br J Clin Pharmacol. 82:943–956. 2016. View Article : Google Scholar : PubMed/NCBI
19	Yang SX, Polley E and Lipkowitz S: New insights on PI3K/AKT pathway alterations and clinical outcomes in breast cancer. Cancer Treat Rev. 45:87–96. 2016. View Article : Google Scholar : PubMed/NCBI
20	Chen H, Zhou L, Wu X, Li R, Wen J, Sha J and Wen X: The PI3K/AKT pathway in the pathogenesis of prostate cancer. Front Biosci. 21:1084–1091. 2016. View Article : Google Scholar
21	Foster K, Wang Y, Zhou D and Wright C: Dependence on PI3K/Akt signaling for malignant rhabdoid tumor cell survival. Cancer Chemother Pharmacol. 63:783–791. 2009. View Article : Google Scholar : PubMed/NCBI
22	Magee JA, Araki T, Patil S, Ehrig T, True L, Humphrey PA, Catalona WJ, Watson MA and Milbrandt J: Expression profiling reveals hepsin overexpression in prostate cancer. Cancer Res. 61:5692–5696. 2001.PubMed/NCBI
23	Tomlins SA, Mehra R, Rhodes DR, Cao X, Wang L, Dhanasekaran SM, Kalyana-Sundaram S, Wei JT, Rubin MA, Pienta KJ, et al: Integrative molecular concept modeling of prostate cancer progression. Nat Genet. 39:41–51. 2007. View Article : Google Scholar : PubMed/NCBI
24	Wiegert JS and Bading H: Activity-dependent calcium signaling and ERK-MAP kinases in neurons: A link to structural plasticity of the nucleus and gene transcription regulation. Cell Calcium. 49:296–305. 2011. View Article : Google Scholar : PubMed/NCBI
25	Müller I, Lipp P and Thiel G: Ca²⁺ signaling and gene transcription in glucose-stimulated insulinoma cells. Cell Calcium. 52:137–151. 2012. View Article : Google Scholar : PubMed/NCBI
26	Monteith GR, McAndrew D, Faddy HM and Roberts-Thomson SJ: Calcium and cancer: Targeting Ca²⁺ transport. Nat Rev Cancer. 7:519–530. 2007. View Article : Google Scholar : PubMed/NCBI
27	Zhu M, Chen L, Zhao P, Zhou H, Zhang C, Yu S, Lin Y and Yang X: Store-operated Ca²⁺ entry regulates glioma cell migration and invasion via modulation of Pyk2 phosphorylation. J Exp Clin Cancer Res. 33:982014. View Article : Google Scholar : PubMed/NCBI
28	Umemura M, Baljinnyam E, Feske S, De Lorenzo MS, Xie LH, Feng X, Oda K, Makino A, Fujita T, Yokoyama U, et al: Store-operated Ca²⁺ entry (SOCE) regulates melanoma proliferation and cell migration. PLoS One. 9:e892922014. View Article : Google Scholar : PubMed/NCBI
29	Wu Z, Qing J, Xia Y, Wang K and Zhang F: Suppression of stromal interaction molecule 1 inhibits SMMC7721 hepatocellular carcinoma cell proliferation by inducing cell cycle arrest. Biotechnol Appl Biochem. 62:107–111. 2015. View Article : Google Scholar : PubMed/NCBI
30	Xia J, Wang H, Huang H, Sun L, Dong S, Huang N, Shi M, Bin J, Liao Y and Liao W: Elevated Orai1 and STIM1 expressions upregulate MACC1 expression to promote tumor cell proliferation, metabolism, migration, and invasion in human gastric cancer. Cancer Lett. 381:31–40. 2016. View Article : Google Scholar : PubMed/NCBI
31	Xu Y, Zhang S, Niu H, Ye Y, Hu F, Chen S, Li X, Luo X, Jiang S, Liu Y, et al: STIM1 accelerates cell senescence in a remodeled microenvironment but enhances the epithelial-to-mesenchymal transition in prostate cancer. Sci Rep. 5:117542015. View Article : Google Scholar : PubMed/NCBI
32	Zhang Y, Zhang T, Wu C, Xia Q and Xu D: ASIC1a mediates the drug resistance of human hepatocellular carcinoma via the Ca²⁺/PI3-kinase/AKT signaling pathway. Lab Invest. 97:53–69. 2017. View Article : Google Scholar : PubMed/NCBI
33	Li GW, Xing WJ, Bai SZ, Hao JH, Guo J, Li HZ, Li HX, Zhang WH, Yang BF, Wu LY, et al: The calcium-sensing receptor mediates hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells through MEK1/ERK1,2 and PI3K pathways. Basic Clin Pharmacol Toxicol. 108:185–193. 2011. View Article : Google Scholar : PubMed/NCBI
34	Divolis G, Mavroeidi P, Mavrofrydi O and Papazafiri P: Differential effects of calcium on PI3K-Akt and HIF-1α survival pathways. Cell Biol Toxicol. 32:437–449. 2016. View Article : Google Scholar : PubMed/NCBI
35	Liu ZM, Chen GG, Vlantis AC, Tse GM, Shum CK and van Hasselt CA: Calcium-mediated activation of PI3K and p53 leads to apoptosis in thyroid carcinoma cells. Cell Mol Life Sci. 64:1428–1436. 2007. View Article : Google Scholar : PubMed/NCBI
36	Wang C, Chi Y, Li J, Miao Y, Li S, Su W, Jia S, Chen Z, Du S, Zhang X, et al: FAM3A activates PI3K p110α/Akt signaling to ameliorate hepatic gluconeogenesis and lipogenesis. Hepatology. 59:1779–1790. 2014. View Article : Google Scholar : PubMed/NCBI
37	Danciu TE, Adam RM, Naruse K, Freeman MR and Hauschka PV: Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Lett. 536:193–197. 2003. View Article : Google Scholar : PubMed/NCBI
38	Ke L, Xiang Y, Guo X, Lu J, Xia W, Yu Y, Peng Y, Wang L, Wang G, Ye Y, et al: c-Src activation promotes nasopharyngeal carcinoma metastasis by inducing the epithelial-mesenchymal transition via PI3K/Akt signaling pathway: A new and promising target for NPC. Oncotarget. 7:28340–28355. 2016. View Article : Google Scholar : PubMed/NCBI
39	Niessner H, Schmitz J, Tabatabai G, Schmid AM, Calaminus C, Sinnberg T, Weide B, Eigentler TK, Garbe C, Schittek B, et al: PI3K pathway inhibition achieves potent antitumor activity in melanoma brain metastases in vitro and in vivo. Clin Cancer Res. 22:5818–5828. 2016. View Article : Google Scholar : PubMed/NCBI
40	Kim MS, Lee WS, Jeong J, Kim SJ and Jin W: Induction of metastatic potential by TrkB via activation of IL6/JAK2/STAT3 and PI3K/AKT signaling in breast cancer. Oncotarget. 6:40158–40171. 2015. View Article : Google Scholar : PubMed/NCBI
41	Mungai PT, Waypa GB, Jairaman A, Prakriya M, Dokic D, Ball MK and Schumacker PT: Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels. Mol Cell Biol. 31:3531–3545. 2011. View Article : Google Scholar : PubMed/NCBI
42	Sundivakkam PC, Natarajan V, Malik AB and Tiruppathi C: Store-operated Ca²⁺ entry (SOCE) induced by protease-activated receptor-1 mediates STIM1 protein phosphorylation to inhibit SOCE in endothelial cells through AMP-activated protein kinase and p38β mitogen-activated protein kinase. J Biol Chem. 288:17030–17041. 2013. View Article : Google Scholar : PubMed/NCBI