Int J Biol Sci 2019; 15(12):2522-2537. doi:10.7150/ijbs.35563

Research Paper

GATA Binding Protein 3 Boosts Extracellular ATP Hydrolysis and Inhibits Metastasis of Breast Cancer by Up-regulating Ectonucleoside Triphosphate Diphosphohydrolase 3

Meifang Li1,2, Yuzhu Qi1,2, Min Chen3, Zun Wang1,2, De Zeng4, Yingsheng Xiao5, Shaozhong Li1,2, Haoyu Lin6, Xiaolong Wei7, Guojun Zhang3,1✉

1. ChangJiang Scholar's Laboratory of Shantou University Medical College, 22 Xinling Road, Shantou, China
2. The Breast Center, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, China
3. The Cancer Center and the Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, 2000 East Xiang'an Rd, Xiang'an, Xiamen, China
4. Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, China
5. Department of Thyroid Surgery, Central Hospital of Shantou, 114 Waima Road, Shantou, China
6. Department of Breast and Thyroid Surgery, the First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, China
7. Department of Pathology, Cancer Hospital of Shantou University Medical College, 7 Raoping Road, Shantou, China

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Citation:
Li M, Qi Y, Chen M, Wang Z, Zeng D, Xiao Y, Li S, Lin H, Wei X, Zhang G. GATA Binding Protein 3 Boosts Extracellular ATP Hydrolysis and Inhibits Metastasis of Breast Cancer by Up-regulating Ectonucleoside Triphosphate Diphosphohydrolase 3. Int J Biol Sci 2019; 15(12):2522-2537. doi:10.7150/ijbs.35563. Available from http://www.ijbs.com/v15p2522.htm

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Abstract

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.

Keywords: Breast Cancer, GATA3, ENTPD3, Extracellular ATP, Metastasis