Regional Activation of Myosin II in Cancer Cells Drives Tumor Progression via a Secretory Cross-Talk with the Immune Microenvironment

Cell. 2019 Feb 7;176(4):757-774.e23. doi: 10.1016/j.cell.2018.12.038. Epub 2019 Jan 31.


ROCK-Myosin II drives fast rounded-amoeboid migration in cancer cells during metastatic dissemination. Analysis of human melanoma biopsies revealed that amoeboid melanoma cells with high Myosin II activity are predominant in the invasive fronts of primary tumors in proximity to CD206+CD163+ tumor-associated macrophages and vessels. Proteomic analysis shows that ROCK-Myosin II activity in amoeboid cancer cells controls an immunomodulatory secretome, enabling the recruitment of monocytes and their differentiation into tumor-promoting macrophages. Both amoeboid cancer cells and their associated macrophages support an abnormal vasculature, which ultimately facilitates tumor progression. Mechanistically, amoeboid cancer cells perpetuate their behavior via ROCK-Myosin II-driven IL-1α secretion and NF-κB activation. Using an array of tumor models, we show that high Myosin II activity in tumor cells reprograms the innate immune microenvironment to support tumor growth. We describe an unexpected role for Myosin II dynamics in cancer cells controlling myeloid function via secreted factors.

Keywords: NF-κB; ROCK-Myosin II; macrophages; protein secretion; rounded-amoeboid melanoma cells; tumor invasive front.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement / immunology
  • Cell Movement / physiology*
  • Cytoskeletal Proteins
  • Female
  • Humans
  • Interleukin-1alpha / metabolism
  • Male
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Middle Aged
  • Myosin Type II / metabolism*
  • NF-kappa B / metabolism
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Phosphorylation
  • Proteomics
  • Receptor Cross-Talk / physiology
  • Signal Transduction
  • Tumor Microenvironment / immunology


  • Cytoskeletal Proteins
  • Interleukin-1alpha
  • NF-kappa B
  • Myosin Type II