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

作者：Bonan Stephanie; Albrengues Jean; Grasset Eloise; Kuzet Sanya Eduarda; Nottet Nicolas; Bourget Isabelle; Bertero Thomas; Mari Bernard; Meneguzzi Guerrino; Gaggioli Cedric^*

来源：Oncotarget, 2017, 8(1): 1304-1320.

DOI：10.18632/oncotarget.13610

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

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.

• 出版日期2017-1-3