The ETS transcription factor Elf5 drives lung metastasis in luminal breast cancer via recruitment of Gr-1+CD11b+ myeloid derived suppressor cells [acute]

Elf5 expression in mammary progenitor cells regulates a cell fate decision that establishes the alveolar cell lineage. In luminal breast cancer cells, increased Elf5 expression suppressed estrogen receptor and FoxA1 expression and was implicated in the acquisition of resistance to the cytostatic effects of antiestrogen therapy. We show that in the PyMT model of luminal breast cancer, increased Elf5 expression drives lung metastasis by recruiting myeloid-derived suppressor cells, and that this activity overcomes the epithelializing influence of Elf5. Breast cancer expression signatures identify a similar process in humans, and increased Elf5 immunohistochemical staining predicts poor prognosis in the luminal A subgroup. Thus Elf5 may promote escape from hormonal therapy and drive metastasis in luminal breast cancer.

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Gallego-Ortega D, Ledger A, Roden DL, Law AM, Magenau A, Kikhtyak Z, Cho C, Allerdice SL, Lee HJ, Valdes-Mora F, Herrmann D, Salomon R, Young AI, Lee BY, Sergio CM, Kaplan W, Piggin C, Conway JR, Rabinovich B, Millar EK, Oakes SR, Chtanova T, Swarbrick A, Naylor MJ, O'Toole S, Green AR, Timpson P, Gee JM, Ellis IO, Clark SJ, Ormandy CJ