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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism*
  • Cell Movement
  • Humans
  • Janus Kinase 1 / metabolism*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction*
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • rho-Associated Kinases / metabolism*


  • STAT3 Transcription Factor
  • Actomyosin
  • JAK1 protein, human
  • Janus Kinase 1
  • rho-Associated Kinases