Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts
| Autor: | Stephanie Bonan, Eloise M. Grasset, Cedric Gaggioli, Isabelle Bourget, Nicolas Nottet, Bernard Mari, Sanya-Eduarda Kuzet, Guerrino Meneguzzi, Thomas Bertero, Jean Albrengues |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty carcinoma-associated fibroblast Stromal cell Myosin light-chain kinase ICAM-1 medicine.medical_treatment extracellular matrix macromolecular substances Biology Contractility Extracellular matrix 03 medical and health sciences 0302 clinical medicine medicine Tumor Microenvironment Humans Fibroblast Cells Cultured Tumor microenvironment Actomyosin Fibroblasts Intercellular Adhesion Molecule-1 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure Cytokine Oncology inflammation Head and Neck Neoplasms 030220 oncology & carcinogenesis Stromal Cells Proto-oncogene tyrosine-protein kinase Src Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Stephanie Bonan 1 , Jean Albrengues 1 , Eloise Grasset 1 , Sanya-Eduarda Kuzet 1 , Nicolas Nottet 2 , Isabelle Bourget 1 , Thomas Bertero 1 , Bernard Mari 2 , Guerrino Meneguzzi 1 , Cedric Gaggioli 1 1 INSERM U1081, CNRS UMR7284, Institute for Research on Cancer and Aging, Nice (IRCAN), University of Nice Sophia Antipolis, Medical School, F-06107, Nice, France 2 Institut de Pharmacologie Moleculaire et Cellulaire (IPMC), CNRS UMR7275, Sophia-Antipolis, France Correspondence to: Cedric Gaggioli, email: gaggioli@unice.fr Keywords: carcinoma-associated fibroblast, ICAM-1, tumor microenvironment, inflammation, extracellular matrix Received: July 13, 2016 Accepted: November 07, 2016 Published: November 25, 2016 ABSTRACT Acto-myosin contractility in carcinoma-associated fibroblasts leads to assembly of the tumor extracellular matrix. The pro-inflammatory cytokine LIF governs fibroblast activation in cancer by regulating the myosin light chain 2 activity. So far, however, how LIF mediates cytoskeleton contractility remains unknown. Using phenotypic screening assays based on knock-down of LIF-dependent genes in fibroblasts, we identified the glycoprotein ICAM-1 as a crucial regulator of stroma fibroblast proinvasive matrix remodeling. We demonstrate that the membrane-bound ICAM-1 isoform is necessary and sufficient to promote inflammation-dependent extracellular matrix contraction, which favors cancer cell invasion. Indeed, ICAM-1 mediates generation of acto-myosin contractility downstream of the Src kinases in stromal fibroblasts. Moreover, acto-myosin contractility regulates ICAM-1 expression by establishing a positive feedback signaling. Thus, targeting stromal ICAM-1 might constitute a possible therapeutic mean to counteract tumor cell invasion and dissemination. |
| Databáze: | OpenAIRE |
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