Here, we report that the predictions from these studies are confirmed in an immunocompetent mouse model in vivo: collagen-I accumulation promoted ERK1/2 and AKT activation and decreased STAT5 phosphorylation in PRL-induced ERα + mammary carcinomas, driving local invasion of the primary tumor, realigning collagen fibers, mobilizing tumor epithelia, and enhancing pulmonary metastases. The gene discussed is PRL; the disease is neoplasm.