RT Journal Article SR Electronic T1 Laminin α1 orchestrates VEGFA functions in the ecosystem of colorectal carcinoma JF bioRxiv FD Cold Spring Harbor Laboratory SP 099465 DO 10.1101/099465 A1 E. Mammadova-Bach A1 T. Rupp A1 C. Spenlé A1 I. Jivkov A1 P. Shankaranarayanan A1 A. Klein A1 L. Pisarsky A1 A. Méchine-Neuville A1 G. Cremel A1 M. Kedinger A1 O. De Wever A1 N. Ambartsumian A1 S. Robine A1 E. Pencreach A1 D. Guenot A1 J.G. Goetz A1 P. Simon-Assmann A1 G. Orend A1 O. Lefebvre YR 2017 UL http://biorxiv.org/content/early/2017/01/10/099465.abstract AB Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumorstroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation. A gene signature comprising LAMA1, ITGB1, ITGA2, CXCR4 and VEGFA has negative predictive value in colon cancer. Together, this information opens novel opportunities for diagnosis and anti-cancer targeting.BMbasement membraneECMextracellular matrixLMlamininvLMα1villin-LMα1 transgenic miceCAFscancer-associated fibroblastsIFimmunofluorescenceVEGFvascular endothelial growth factor.