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前蛋白转化酶枯草溶菌素/kexin 6型激活细胞外信号调节激酶1/2和Wnt家族成员3A通路,并促进乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。

Proprotein convertase subtilisin/kexin type 6 activates the extracellular signal-regulated kinase 1/2 and Wnt family member 3A pathways and promotes proliferation, migration and invasion of breast cancer MDA-MB-231 cells.

作者信息

Wang Ping, Wang Feifei, Wang Lin, Pan Jihong

机构信息

Anesthesia Department, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250000, P.R. China.

Shandong Medicinal Biotechnology Center, Jinan, Shandong 250062, P.R. China.

出版信息

Oncol Lett. 2018 Jul;16(1):145-150. doi: 10.3892/ol.2018.8654. Epub 2018 May 7.

Abstract

Breast cancer progression results from the acquisition of genetic and epigenetic alterations that promote tumor cell proliferation and survival. Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a proteinase that regulates the proteolytic activity of various precursor proteins as well as protein maturation. PCSK6 also influences cancer cell proliferation, invasion and migration. Therefore, to investigate the effects of PCSK6 in breast cancer, human breast cancer MDA-MB-231 cells were treated with recombinant human PCSK6 . Treatment with recombinant PCSK6 significantly increased the proliferation, invasion and migration abilities of MDA-MB-231 cells. In addition, PCSK6 treatment reduced cell cycle arrest and prevented apoptosis of MDA-MB-231 cells. This provides further support for the hypothesis that PCSK6 serves a role in promoting tumor cell proliferation. PCSK6 treatment also increased the expression of phosphorylated extracellular signal-regulated kinase 1/2 and Wnt family member 3A, suggesting that these pathways are activated by PCSK6. The results of the present study suggested that PCSK6 may promote the proliferation of breast cancer MDA-MB-231 cells by disturbing cell cycle arrest via the mitogen-activated protein kinase pathway. Therefore, PCSK6 may be a potential therapeutic target for breast cancer.

摘要

乳腺癌的进展源于获得促进肿瘤细胞增殖和存活的遗传和表观遗传改变。前蛋白转化酶枯草杆菌蛋白酶/kexin 6型(PCSK6)是一种蛋白酶,可调节各种前体蛋白的蛋白水解活性以及蛋白质成熟。PCSK6还影响癌细胞的增殖、侵袭和迁移。因此,为了研究PCSK6在乳腺癌中的作用,用人重组PCSK6处理人乳腺癌MDA-MB-231细胞。用重组PCSK6处理显著提高了MDA-MB-231细胞的增殖、侵袭和迁移能力。此外,PCSK6处理减少了细胞周期停滞并防止了MDA-MB-231细胞的凋亡。这为PCSK6在促进肿瘤细胞增殖中起作用的假说提供了进一步支持。PCSK6处理还增加了磷酸化细胞外信号调节激酶1/2和Wnt家族成员3A的表达,表明这些途径被PCSK6激活。本研究结果表明,PCSK6可能通过有丝分裂原活化蛋白激酶途径干扰细胞周期停滞来促进乳腺癌MDA-MB-231细胞的增殖。因此,PCSK6可能是乳腺癌的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63c/6006270/3e2ff2535c4f/ol-16-01-0145-g00.jpg

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