Gao Hui, Zhong Feng, Xie Jing, Peng Jianjun, Han Zhiwu
Qingdao University Qingdao, Shandong 266071, China.
College of Life Sciences, Chongqing Normal University Chongqing 401331, China.
Am J Cancer Res. 2016 Jan 15;6(2):425-39. eCollection 2016.
Pituitary tumor transforming gene (PTTG) is a novel oncogene that is expressed at higher level in most of the tumors. PTTG overexpression correlates with lymph node infiltration and a higher degree of tumor recurrence in breast cancer. However, the cellular functions and precise signals elicited by PTTG in breast cancer are not fully understood. Here, we established a breast cancer cell line which stably overexpressed PTTG. In vitro experiments showed that overexpression of PTTG in MCF-7 cells was associated with enhanced cell migration and invasion as well as EMT. Our results also demonstrated that PTTG overexpression correlated with elevated EMMPRIN level, which mediated the enhanced cell migration, invasion and EMT. Moreover, our findings suggested that PTTG enhances metastatic potential of breast cancer cells by inducing EMMPRIN through activating FAK/Akt/mTOR pathway. Our findings may lead to a better understanding of the biological effect of PTTG and provide mechanistic insights for developing potential therapeutic strategies for inhibiting the invasion and metastasis of breast cancer.
垂体肿瘤转化基因(PTTG)是一种新型癌基因,在大多数肿瘤中均呈高水平表达。PTTG的过表达与乳腺癌的淋巴结浸润及较高的肿瘤复发率相关。然而,PTTG在乳腺癌中的细胞功能及引发的精确信号尚未完全明确。在此,我们建立了一种稳定过表达PTTG的乳腺癌细胞系。体外实验表明,MCF-7细胞中PTTG的过表达与细胞迁移、侵袭能力增强以及上皮-间质转化(EMT)相关。我们的结果还表明,PTTG的过表达与细胞外基质金属蛋白酶诱导因子(EMMPRIN)水平升高相关,EMMPRIN介导了细胞迁移、侵袭及EMT能力的增强。此外,我们的研究结果提示,PTTG通过激活黏着斑激酶(FAK)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路诱导EMMPRIN,从而增强乳腺癌细胞的转移潜能。我们的研究结果可能有助于更好地理解PTTG的生物学效应,并为开发抑制乳腺癌侵袭和转移的潜在治疗策略提供机制性见解。