Expression and regulation of monocarboxylate transporters 4(MCT4) in prostate cancer

doi:10.3969/j.issn.1006-7795.2019.01.011

Abstract

Abstract: Objective To investigate the expression and clinical significance of monocarboxylate transporters 4(MCT4) in prostate cancer(PCa), and explore the regulation mechanism of MCT4 in PCa. Methods The expression of MCT4 was detected by immunohistochemistry in PCa, benign prostatic hyperplasia(BPH) and para-carcinoma tissues(PCT). The relation between the expression and clinicopathological changes was analyzed statistically. The expression of MCT4 was examined with Western blotting in prostate cancer cells. The effects on N-cadherin, E-cadherin and pERK1/2 by inhibition of MCT4 was also analyzed. Results The expression of MCT4 in PCa was significantly higher than those in BPH and PCT (P=0.003). Furthermore, the increased expression of MCT4 protein was significantly associated with the presence of lymph node metastasis of PCa(P=0.022). The Western blotting indicated that, the expression of MCT4 protein was higher in PC3 and DU145 than in RWPE-1 and LNCap cell lines. With inhibition of MCT4, the level of N-cadherin and pERK1/2 was decreased, while that of E-cadherin was increased. Conclusion The expression of MCT4 may be involved in the regulation of epithelial-mesenchymal transition (EMT) and ERK1/2, and it is closely related to the metastasis of PCa. The expression of MCT4 has significant clinical implications for diagnosis and treatment of PCa.

Key words: prostate cancer, monocarboxylate transporters 4, lymph node metastasis, regulation

CLC Number:

R737.25

Ping Hao, Ma Linxiang, Wang Mingshuai, Long Jun, Niu Yinong, Liu Yuexin, Xing Nianzeng. Expression and regulation of monocarboxylate transporters 4(MCT4) in prostate cancer[J]. Journal of Capital Medical University, 2019, 40(1): 59-64.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2019.01.011

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2019/V40/I1/59

References

[1] Siegel R L, Miller K D, Jemal A. Cancer statistics, 2018[J]. CA Cancer J Clin,2018, 68(1):7-30.
[2] Choi J W, Kim Y, Lee J H, et al. Prognostic significance of lactate/proton symporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder[J]. Urology, 2014, 84(1):245.e9-15.
[3] Kim H K, Lee I, Bang H, et al. MCT4 expression is a potential therapeutic target in colorectal cancer with peritoneal carcinomatosis[J]. Mol Cancer Ther, 2018, 17(4):838-848.
[4] Pértega-Gomes N, Vizcaíno J R, Attig J, et al. A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancer[J]. BMC Cancer, 2014, 14:352.
[5] Li Z, Wu Q, Sun S, et al. Monocarboxylate transporters in breast cancer and adipose tissue are novel biomarkers and potential therapeutic targets[J]. Biochem Biophys Res Commun, 2018, 501(4):962-967.
[6] Sanità P, Capulli M, Teti A, et al. Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression[J]. BMC Cancer, 2014,14:154.
[7] 薛炜,邱建新,桑楠,等.Oct4蛋白对前列腺癌雄激素剥夺治疗后进展速度的预测价值分析[J].解放军医药杂志,2018,30(7):22-25,30.
[8] Ceder Y, Bjartell A, Culig Z, et al. The molecular evolution of castration-resistant prostate cancer[J]. Eur Urol Focus, 2016, 2(5):506-513.
[9] Sormendi S, Wielockx B. Hypoxia pathway proteins as central mediators of metabolism in the tumor cells and their microenvironment[J]. Front Immunol, 2018, 9:40.
[10] Baltazar F, Pinheiro C, Morais-Santos F, et al. Monocarboxylate transporters as targets and mediators in cancer therapy response[J]. Histol Histopathol,2014, 29(12):1511-1524.
[11] Zhu J, Wu Y N, Zhang W, et al. Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients[J]. PLoS One, 2014, 9(1):e87904.
[12] Bovenzi C D, Hamilton J, Tassone P, et al. Prognostic indications of elevated MCT4and CD147 across cancer types:a Meta-analysis[J]. Biomed Res Int, 2015, 2015:242437.
[13] Choi S Y, Xue H, Wu R, et al. The MCT4 Gene:a novel, potential target for therapy of advanced prostate cancer[J]. Clin Cancer Res, 2016,22(11):2721-2733.
[14] Kelsey R. Prostate cancer:MCT4 is a novel target for prostate cancer[J]. Nat Rev Urol,2016, 13(3):123.
[15] Gao H J, Zhao M C, Zhang Y J, et al. Monocarboxylate tansporter 4 predicts poor prognosis in hepatocellular carcinoma and is associate with cell proliferation andmigration[J]. J Cancer Res Clin Oncol, 2015,141(7):1151-1162.
[16] Todenhöfer T, Seiler R, Stewart C, et al. Selective inhibition of the lactate transporter MCT4 reduces growth of invasive bladder cancer[J]. Mol Cancer Ther,2018, 17(12):2746-2755.
[17] Gerlinger M, Santos C R, Spencer-Dene B, et al. Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target[J]. J Pathol, 2012, 227(2):146-156.
[18] Wilde L, Roche M, Domingo-Vidal M, et al. Metabolic coupling and the reverse warburg effect in cancer:Implications for novel biomarker and anticancer agent development[J]. Semin Oncol, 2017, 44(3):198-203.
[19] Choi S Y C, Ettinger S L, Lin D, et al. Targeting MCT4 to reduce lactic acid secretion and glycolysis for treatment of neuroendocrine prostate cancer[J]. Cancer Med, 2018,7(7):3385-3392.