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

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.
AuthorsVictoria Sanz-Moreno, Cedric Gaggioli, Maggie Yeo, Jean Albrengues, Fredrik Wallberg, Amaya Viros, Steven Hooper, Richard Mitter, Chloé C Féral, Martin Cook, James Larkin, Richard Marais, Guerrino Meneguzzi, Erik Sahai, Chris J Marshall
JournalCancer cell (Cancer Cell) Vol. 20 Issue 2 Pg. 229-45 (Aug 16 2011) ISSN: 1878-3686 [Electronic] United States
PMID21840487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • STAT3 Transcription Factor
  • Actomyosin
  • JAK1 protein, human
  • Janus Kinase 1
  • rho-Associated Kinases
  • Actomyosin (metabolism)
  • Cell Movement
  • Humans
  • Janus Kinase 1 (metabolism)
  • Melanoma (metabolism, pathology)
  • Neoplasms (metabolism, pathology)
  • STAT3 Transcription Factor (metabolism)
  • Signal Transduction
  • Stromal Cells (metabolism, pathology)
  • rho-Associated Kinases (metabolism)

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