Metal transporter CNNM3

It exists an inverse correlation between the propensity of the CNBH domains to dimerize and the ability of CNNMs to mediate Mg2+ efflux, which has been proved with analytical ultracentrifugation experiments.

Magnesium (Mg2+) is one of the most abundants cations inside cells and it is essential for an extensive variety of biochemical processes that occur in our organisms: energy metabolism, maintenance of the stability of DNA, synthesis of proteins, and over six hundred enzymatic reactions.

PRLs (mainly PRL-2), important in the metastasis of several human cancers whose molecular base of operation remains confusing, control the intracellular levels of magnesium forming a complex with a set of amino acid residing in the Bateman module (CBS- pair domain) on the CNNM3 magnesium transporter.

[8] Starting from an orthotopic xenotransplant breast cancer model, the in vivo importance of the point mutation D426A (in the position 426, there is a change of an aspartic acid to an alanine) that completely alters the formation of the CNNM3-PRL 2 complex is confirmed.

[9] Overexpression of this CNNM3 binding mutant in cancer cells decreases the proliferation capacity in situations of magnesium shortage and in conditions independent of anchorage growth.

Therefore, using a PRL inhibitor it would be possible to disable the formation of complexes, resulting in a decreased cell proliferation in these types of human cancer.

[11] Nowadays, current treatments against lung cancer involve major remove surgery, followed by radio and chemotherapy.

Some studies have revealed that the expression of Pyrubate dehydrogenase kinase (PDK), which is an enzymatic regulator in some metabolic processes as glycolysis and oxidative phosphorilation, is increased in some tumors in colon or lung cancer.

The expression of this gene is dramatically elevated in high-grade lung adenocarcinoma and could be conversely correlated to the poor prognosis.