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Oncotarget. 2017 Jan 3;8(1):1304-1320. doi: 10.18632/oncotarget.13610.

Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts.

Author information

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 Moléculaire et Cellulaire (IPMC), CNRS UMR7275, Sophia-Antipolis, France.

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.

KEYWORDS:

ICAM-1; carcinoma-associated fibroblast; extracellular matrix; inflammation; tumor microenvironment

PMID:
27901489
PMCID:
PMC5352056
DOI:
10.18632/oncotarget.13610
[Indexed for MEDLINE]
Free PMC Article

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