Membrane-bound ICAM-1 contributes to the onset of proinvasive tumor stroma by controlling acto-myosin contractility in carcinoma-associated fibroblasts.
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| 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.
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| Authors | Stephanie Bonan, Jean Albrengues, Eloise Grasset, Sanya-Eduarda Kuzet, Nicolas Nottet, Isabelle Bourget, Thomas Bertero, Bernard Mari, Guerrino Meneguzzi, Cedric Gaggioli |
| Journal | Oncotarget (Oncotarget) Vol. 8 Issue 1 Pg. 1304-1320 (Jan 03 2017) ISSN: 1949-2553 [Electronic] United States |
| PMID | 27901489 (Publication Type: Journal Article) |
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