title: ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma.
abstract: 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.
authors.affiliation: Oncogene Team, Institute of Cancer Research, Section of Cell and Molecular Biology, Cancer Research UK Tumour Cell Signalling Unit, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sanz-Moreno
authors.forename: Cedric
authors.initials: C
authors.lastname: Gaggioli
authors.forename: Maggie
authors.initials: M
authors.lastname: Yeo
authors.forename: Jean
authors.initials: J
authors.lastname: Albrengues
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wallberg
authors.forename: Amaya
authors.initials: A
authors.lastname: Viros
authors.forename: Steven
authors.initials: S
authors.lastname: Hooper
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.forename: Chloé C
authors.initials: CC
authors.lastname: Féral
authors.forename: Martin
authors.initials: M
authors.lastname: Cook
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.forename: Richard
authors.initials: R
authors.lastname: Marais
authors.forename: Guerrino
authors.initials: G
authors.lastname: Meneguzzi
authors.forename: Erik
authors.initials: E
authors.lastname: Sahai
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Marshall
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D002465:Cell Movement; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; D000205:Actomyosin; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D054460:rho-Associated Kinases