Oncogene Team, Institute of Cancer Research, Section of Cell and Molecular Biology, Cancer Research UK Tumour Cell Signalling Unit, 237 Fulham Road, London SW3 6JB, UK.
Cancer Cell. 2011 Aug 16;20(2):229-45. doi: 10.1016/j.ccr.2011.06.018.
Proinflammatory cytokines are frequently observed in the tumor microenvironment, and chronic inflammation is involved in cancer initiation and progression. We show that cytokine signaling through the receptor subunit GP130-IL6ST and the kinase JAK1 generates actomyosin contractility through Rho-kinase dependent signaling. This pathway generates contractile force in stromal fibroblasts to remodel the extracellular matrix to create tracks for collective migration of squamous carcinoma cells and provides the high levels of actomyosin contractility required for migration of individual melanoma cells in the rounded, "amoeboid" mode. Thus, cytokine signaling can generate actomyosin contractility in both stroma and tumor cells. Strikingly, actomyosin contractility itself positively modulates activity of the transcription factor STAT3 downstream of JAK1, demonstrating positive feedback within the signaling network.
促炎细胞因子在肿瘤微环境中经常被观察到，慢性炎症参与癌症的发生和发展。我们表明，通过受体亚基 GP130-IL6ST 和激酶 JAK1 的细胞因子信号转导通过 Rho-激酶依赖性信号转导产生肌动球蛋白收缩。该途径在基质成纤维细胞中产生收缩力，重塑细胞外基质，为鳞状癌细胞的集体迁移创建轨迹，并为个体黑色素瘤细胞以圆形的“阿米巴样”模式迁移提供所需的高水平肌动球蛋白收缩力。因此，细胞因子信号可以在基质和成纤维细胞中产生肌动球蛋白收缩力。引人注目的是，肌动球蛋白收缩本身正向调节 JAK1 下游转录因子 STAT3 的活性，表明信号网络内的正反馈。
