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

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• 作者：Victoria Sanz-Moreno¹ ; ¹² ; ⁹ ; Cedric Gaggioli² ; ³ ; ¹² ; Maggie Yeo¹ ; Jean Albrengues² ; ³ ; Fredrik Wallberg⁴ ; Amaya Viros⁵ ; Steven Hooper⁶ ; Richard Mitter⁷ ; Chloé ;   ; C. Fé ; ral⁸ ; ³ ; Martin Cook¹⁰ ; James Larkin¹¹ ; Richard Marais⁵ ; Guerrino Meneguzzi² ; ³ ; Erik Sahai⁶ ; Chris  ; J. Marshall¹ ; ^{chris.marshall@icr.ac.uk"" rel=""nofollow}
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：16 August 2011
• 年：2011
• 卷：20
• 期：2
• 页码：229-245
• 全文大小：3017 K

文摘

Summary

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.