ROCK and JAK1 Signaling Cooperate to Control Actomyosin Contractility in Tumor Cells and Stroma
Open accessAbstract
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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Various inflammatory modulators can promote CAF activation, with IL-1 acting through NF-κB and IL-6 acting primarily on STAT transcription factors.
“Various inflammatory modulators can promote CAF activation, with interleukin-1 (IL-1) acting through NF-κB and IL-6 acting primarily on signal transducer and activator of transcription (STAT) transcription factors57,58.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [58]
Cites
limma: Linear Models for Microarray Data
Smyth, G. K. (2005) · Statistics for Biology and Health · doi:10.1007/0-387-29362-0_23 · Cited by 5,796 · see citing works
Gaggioli, C., Hooper, S., Hidalgo-Carcedo, C., Grosse, R., Marshall, J. F., Harrington, K., & Sahai, E. (2007) · Nature Cell Biology · doi:10.1038/ncb1658 · Cited by 1,589 · see citing works
Tumor Self-Seeding by Circulating Cancer Cells
Kim, M.-Y., Oskarsson, T., Acharyya, S., Nguyen, D. X., Zhang, X. H.-F., Norton, L., & Massagué, J. (2009) · Cell · doi:10.1016/j.cell.2009.11.025 · Cited by 1,335 · see citing works
Identification of novel direct Stat3 target genes for control of growth and differentiation
Snyder, M., Huang, X.-Y., & Zhang, J. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706976200 · Cited by 108 · see citing works
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A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863 · see citing works
Self-citationMao, X., Xu, J., Wang, W., Liang, C., Hua, J., Liu, J., Zhang, B., Meng, Q., Yu, X., & Shi, S. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01428-1 · Cited by 2,290 · see citing works
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer
Wu, F., Yang, J., Liu, J., Wang, Y., Mu, J., Zeng, Q., Deng, S., & Zhou, H. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00641-0 · Cited by 773 · see citing works
Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy
Swartz, M. A., Iida, N., Roberts, E. W., Sangaletti, S., Wong, M. H., Yull, F. E., Coussens, L. M., & DeClerck, Y. A. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0122 · Cited by 542 · see citing works
Two-photon excitation microscopy for the study of living cells and tissues
Benninger, R. K. P., & Piston, D. W. (2013) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb0411s59 · Cited by 311 · see citing works
Vennin, C., Mélénec, P., Rouet, R., Nobis, M., Cazet, A. S., Murphy, K. J., Herrmann, D., Reed, D. A., Lucas, M. C., Warren, S. C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10968-6 · Cited by 268 · see citing works
Zanin-Zhorov, A., Weiss, J. M., Nyuydzefe, M. S., Chen, W., Scher, J. U., Mo, R., Depoil, D., Rao, N., Liu, B., Wei, J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414189111 · Cited by 262 · see citing works
Carcinoma‐associated fibroblasts: Non‐neoplastic tumour‐promoting mesenchymal cells
Polanska, U. M., & Orimo, A. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24347 · Cited by 208 · see citing works
Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy
Raskov, H., Orhan, A., Gaggar, S., & Gögenur, I. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.668731 · Cited by 150 · see citing works
- Authors
- Sanz-Moreno, V., Gaggioli, C., Yeo, M., Albrengues, J., Wallberg, F., Viros, A., Hooper, S., Mitter, R., Féral, C. C., Cook, M., Larkin, J., Marais, R., Meneguzzi, G., Sahai, E., & Marshall, C. J.
- Affiliations
- Institute of Cancer Research (GB)
- Inserm (FR)
- Cancer Research UK (GB)
- Royal Surrey County Hospital (GB)
- Royal Marsden NHS Foundation Trust (GB)
- Corresponding author
- Marshall, Chris J.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 20
- Issue
- 2
- Pages
- 229-245
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2031409539
- Cited by
- 409
- References
- 4
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 21 · 2023: 27 · 2022: 35 · 2021: 38 · 2020: 43 · 2019: 19 · 2018: 24 · 2017: 25 · 2016: 36 · 2015: 26 · 2014: 33 · 2013: 21 · 2012: 23
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 716 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Cancer Research UK
- European Commission
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- actomyosin contractility, Rho kinase, ROCK signaling, inflammatory cytokines, tumor microenvironment, stromal fibroblasts, extracellular matrix remodeling, collective cell migration, squamous cell carcinoma, melanoma, amoeboid migration, STAT3, positive feedback loop, chronic inflammation
- MeSH terms
- Actomyosin, Cell Movement, Humans, Melanoma, Neoplasms, Signal Transduction, Stromal Cells, STAT3 Transcription Factor, Janus Kinase 1, rho-Associated Kinases
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