Despite remarkable advancements in our understanding of
breast cancer, it remains the leading cause of
cancer deaths in women. Distant recurrence and
metastasis is the main reason for death due to
breast cancer. It is well recognized that the GATA
binding protein 3 (GATA3), a
transcription factor, is a
tumor suppressor in
breast cancer. To date, the mechanistic molecular details of GATA3 remain elusive, because, as a
transcription factor, it is not a direct executor in physiological and
pathological processes. Here, we demonstrate that GATA3 reduces the
ATP level in the
breast cancer microenvironment and inhibits
breast cancer metastasis by up-regulating ectonucleoside
triphosphate diphosphohydrolase 3 (ENTPD3). The extracellular
ATP concentration is significantly higher in
tumor tissues than in normal tissues and promotes the migration of
cancer cells from the primary site. ENTPD3 hydrolyzes
ATP in tumor microenvironment and suppresses
breast cancer metastasis. Furthermore, ENTPD3 inhibits epithelial-to-mesenchymal transition, a key program responsible for the development of metastatic disease. These findings provide novel insights into the
tumor suppressor activity of GATA3.