GATA3 Reprograms Basal Breast Cancer Cells towards a Luminal Subtype and Inhibits Metastases through Suppression of Lysyl Oxidase

The transcription factor GATA3 is essential for luminal cell differentiation during mammary gland development and critical for formation of the luminal subtypes of breast cancer. Ectopic expression of GATA3 promoted global alterations of the transcriptome of basal triple-negative breast cancer cells resulting in molecular and cellular changes associated with a more differentiated, luminal tumor subtype and a concomitant reduction in primary tumor growth, lung metastasis, and macrophage recruitment at the metastatic site. Importantly, we demonstrate that the inhibition of metastases by GATA3 results from the suppression of lysyl oxidase (LOX) expression, a metastasis promoting matrix protein that affects cell proliferation, cross-linking of extracellular collagen types, and establishment of the metastatic niche.

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Chu IM, Michalowski AM, Hoenerhoff M, Szauter KM, Luger D, Sato M, Flanders K, Oshima A, Csiszar K, Green JE