期刊
CELL BIOLOGY INTERNATIONAL
卷 45, 期 2, 页码 411-421出版社
WILEY
DOI: 10.1002/cbin.11497
关键词
breast cancer; ectophosphatase activity; MDA‐ MB‐ 231
类别
资金
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro [e-26/201.300/2014]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [0012017]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [401134/2014-8]
Breast cancer is associated with genetic mutations that lead to uncontrolled growth of breast cells. Tumor cells have rewired energy metabolism compared to normal cells, with inorganic phosphate playing a crucial role in cancer cell proliferation. Understanding the activity of ectophosphatase can provide insights into cancer cell energy requirements and growth mechanisms.
Breast cancer is one of the most common cancers in the female population worldwide, and its development is thought to be associated with genetic mutations that lead to uncontrolled and accelerated growth of breast cells. This abnormal behavior requires extra energy, and indeed, tumor cells display a rewired energy metabolism compared to normal breast cells. Inorganic phosphate (Pi) is a glycolytic substrate of glyceraldehyde-3-phosphate dehydrogenase and has an important role in cancer cell proliferation. For cells to obtain Pi, ectoenzymes in the plasma membrane with their catalytic site facing the extracellular environment can hydrolyze phosphorylated molecules, and this is an initial and possibly limiting step for the uptake of Pi by carriers that behave as adjuvants in the process of energy harvesting and thus partially contributes to tumor energy requirements. In this study, the activity of an ectophosphatase in MDA-MB-231 cells was biochemically characterized, and the results showed that the activity of this enzyme was higher in the acidic pH range and that the enzyme had a K-m = 4.5 +/- 0.5 mM para-nitrophenylphosphate and a V-max = 2280 +/- 158 nM x h(-1) x mg protein(-1). In addition, classical acid phosphatase inhibitors, including sodium orthovanadate, decreased enzymatic activity. Sodium orthovanadate was able to inhibit ectophosphatase activity while also inhibiting cell proliferation, adhesion, and migration, which are important processes in tumor progression, especially in metastatic breast cancer MDA-MB-231 cells that have higher ectophosphatase activity than MCF-7 and MCF-10 breast cells.
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