Bharti Rashmi, Dey Goutam, Mandal Mahitosh
School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
Cancer Lett. 2016 May 28;375(1):51-61. doi: 10.1016/j.canlet.2016.02.048. Epub 2016 Mar 2.
Interleukin-6 (IL-6) is a cytokine present in tumor microenvironment. Elevated level of IL-6 is associated with cancer cell proliferation, angiogenesis and metastasis through fueling STAT3, MAPK and Akt signaling. It promotes epithelial to mesenchymal transition (EMT) through altered expression of N-cadherin, vimentin, snail, twist and E-cadherin leading to cancer metastasis. IL-6 boosts mammosphere formation, self-renewal of stem cells, stemness properties of cancer cells and recruitment of mesenchymal stem cells. IL-6 is also a contributing factor for multidrug resistance in cancer due to gp130/MAPK/STAT3 mediated activation of transcription factors C/EBPβ/δ, overexpression of p-glycoprotein, EMT transition and expansion of stem cells. The in-depth investigation of IL-6 mediated cellular effects and its signaling pathway can provide the new window for future research and clinical development of IL-6 targeted therapy in cancer. Thus, an overview is delivered in this review deciphering the emerging aspect of the predominant influence of IL-6 in malignant transformation, EMT, cancer-associated stem cells and chemoresistance.
白细胞介素-6（IL-6）是肿瘤微环境中存在的一种细胞因子。IL-6水平升高通过激活信号转导和转录激活因子3（STAT3）、丝裂原活化蛋白激酶（MAPK）和蛋白激酶B（Akt）信号通路，与癌细胞增殖、血管生成和转移相关。它通过改变N-钙黏蛋白、波形蛋白、蜗牛蛋白、Twist蛋白和E-钙黏蛋白的表达促进上皮-间质转化（EMT），从而导致癌症转移。IL-6促进乳腺球形成、干细胞自我更新、癌细胞干性特性以及间充质干细胞募集。由于糖蛋白130（gp130）/MAPK/STAT3介导的转录因子C/EBPβ/δ激活、P-糖蛋白过表达、EMT转变和干细胞扩增，IL-6也是癌症多药耐药的一个促成因素。对IL-6介导的细胞效应及其信号通路的深入研究可为未来癌症IL-6靶向治疗的研究和临床开发提供新的窗口。因此，本综述提供了一个概述，解读了IL-6在恶性转化、EMT、癌症相关干细胞和化疗耐药中的主要影响的新方面。
