H+-dependent inorganic phosphate transporter in breast cancer cells: Possible functions in the tumor microenvironment

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 Km = 4.5 ± 0.5 mM para‐nitrophenylphosphate and a Vmax = 2280 ± 158 nM × h−1 × 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.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Cell lysates were read spectrophotometrically at 570 nm. The results are expressed as a percentage of the control (Lacerda‐Abreu et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ectophosphatase activity in the triple‐negative breast cancer cell line MDA‐MB‐231

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et al. 2020

Resveratrol is an inhibitor of sodium‐dependent inorganic phosphate transport in triple‐negative MDA‐MB‐231 breast cancer cells

Lacerda-Abreu

Russo‐Abrahão

Meyer‐Fernandes

2021

Metastasis is a major cause of death in patients with breast cancer. A growing body of evidence has demonstrated the antitumour effects of resveratrol, a non-flavonoid polyphenol. Resveratrol inhibits metastatic processes, such as the migration and invasion of cancer cells. In several cancer types, the importance of inorganic phosphate (Pi) for tumor progression has been demonstrated. The metastatic process in breast cancer is associated with Na + -dependent Pi transporters. In this study, we demonstrate, for the first time, that resveratrol inhibits the Na + -dependent Pi transporter. Results from kinetic analysis shows that resveratrol inhibits Na +dependent Pi transport non-competitively. Resveratrol also inhibits adhesion/migration in MDA-MB-231 cells, likely related to inhibition of the Na + -dependent Pi transporter.

Elevated extracellular inorganic phosphate inhibits ecto‐phosphatase activity in breast cancer cells: Regulation by hydrogen peroxide

Lacerda‐Abreu,

Meyer‐Fernandes

2023

For cells to obtain inorganic phosphate, ectoenzymes in the plasma membrane, which contain a catalytic site facing the extracellular environment, hydrolyze phosphorylated molecules. In this study, we show that increased Pi levels in the extracellular environment promote a decrease in ecto‐phosphatase activity, which is associated with Pi‐induced oxidative stress. High levels of Pi inhibit ecto‐phosphatase because Pi generates H2O2. Ecto‐phosphatase activity is inhibited by H2O2, and this inhibition is selective for phospho‐tyrosine hydrolysis. Additionally, it is shown that the mechanism of inhibition of ecto‐phosphatase activity involves lipid peroxidation. In addition, the inhibition of ecto‐phosphatase activity by H2O2 is irreversible. These findings have new implications for understanding ecto‐phosphatase regulation in the tumor microenvironment. H2O2 stimulated by high Pi inhibits ecto‐phosphatase activity to prevent excessive accumulation of extracellular Pi, functioning as a regulatory mechanism of Pi variations in the tumor microenvironment.