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Cancer progression requires cells surrounding tumors be reeducated and activated to support tumor growth. Oncogenic signals from malignant cells directly influence stromal composition and activation, but the factors mediating this communication are still not well understood. We have previously shown that the transcription factor POU class 1 homeobox 1 (POU1F1), also known as Pit‐1, induces profound changes on neoplastic cell‐autonomous processes favoring metastasis in human breast cancer. Here we describe for the first time Pit‐1‐mediated paracrine actions on macrophages in the tumor microenvironment by using cell lines in vitro, zebrafish and mouse models in vivo, and samples from human breast cancer patients. Through the release of CXCL12, Pit‐1 in tumor cells was found to mediate the recruitment and polarization of macrophages into tumor‐associated macrophages (TAMs). In turn, TAMs …