ROCK and JAK1 Signaling Cooperate to Control Actomyosin Contractility in Tumor Cells and Stroma

SummaryProinflammatory 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.

► Cytokines signal via JAK1 to actomyosin contractility in tumor cells and stroma
► JAK1 signals to matrix remodelling in CAFs
► JAK1 signals to rounded/amoeboid movement of melanoma cells
► Round cells are found at invasive fronts of melanoma and stain for phospho-STAT3