Increasing appreciation of the importance of tumor-stroma interactions and their reciprocal regulation in cancers has opened up the possibility of novel therapies that target the communication between a tumor and its microenvironment. Using the MMTV-PyMT model of breast cancer, which recapitulates many key stages of the human disease, and genetically modified mice expressing conditionally active ROCK, we have discovered that a novel UPR-mediated mechanism initiated by ROCK activity causes the secretion by tumor cells of the cysteine-rich with EGF-like domains 2 (Creld2) protein. Secreted Creld2 causes the recruitment and education of cancer-associated fibroblasts (CAFs) to promote mammary tumour progression. Creld2-educated, tumour-promoting CAFs produce copious ECM protein, are highly motile, promote migratory behavior in primary mammary tumor cells and drive tumour expansion. This mechanism has significant clinical relevance, with a strong correlation observed between ROCK activation, fibroblast infiltration and CRELD2 expression in clinical samples of invasive breast cancer. Furthermore, elevated CRELD2 expression is associated with reduced 5-year survival in breast cancer patients. We propose that ROCK activity in tumour cells promotes disease progression via a paracrine mechanism that establishes a tumour-promoting microenvironment and that inhibiting the secreted effectors of ROCK that educate cancer-associated fibroblasts may be a novel therapeutic approach to target breast and potentially other cancers.