Mus musculus strain:C57BL/6J | isolate:pulmonary myeloid cells Raw sequence reads

Retinoid X Receptor (RXR) regulates several key functions in myeloid cells, including inflammatory responses, phagocytosis, chemokine expression and angiogenesis. Its importance, however, in the tumor microenvironment is largely unknown. Myeloid cells are the major immune cell types infiltrating many solid tumors, and promote tumor progression by enhancing angiogenesis, cancer cell invasion and suppressing anti-tumor immune responses. In this study, we demonstrate that myeloid-specific deletion of RXR enhances metastasis formation while not affecting primary tumor growth. We show that RXR represses a large set of metastasis-promoting genes in pulmonary myeloid cells, and the relief of repression in the absence of the receptor creates a permissive tissue environment for micrometastasis formation. Our results suggest that the repressive activity of RXR is mediated primarily through direct DNA binding of the receptor together with NCoR and SMRT corepressors and is largely unresponsive to ligand activation. Overall, our results identify RXR as a novel regulator in the myeloid cell-assisted metastatic process and establish lipid-sensing nuclear receptors in the microenvironmental regulation of tumor progression.