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ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma

ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma

Cancer Cell 20(2): 229-245

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.

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Accession: 055338095

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PMID: 21840487

DOI: 10.1016/j.ccr.2011.06.018

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