Ion Channel Protein TRPM7 Required for Breast Tumor Cell Metastasis in a Mouse Xenograft Model

The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. TRPM7 had been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression had not been established.

In a recent study, investigators at Radbound University Medical Center (Nijmegen, the Netherlands) evaluated whether the level of expression of the TRPM7 gene correlated with breast cancer progression.

They reported in the August 7, 2012, online edition of the journal Cancer Research that in primary breast tumors removed at diagnosis from a cohort of 368 women, high levels of expression from the TRPM7 gene were associated with significantly shorter times to both recurrence of disease and occurrence of distant metastases. This association was validated in an independent cohort of 144 breast cancer patients.

Experiments conducted with a mouse xenograft model of human breast cancer revealed that TRPM7 was functionally required for metastasis formation. Mechanistic investigation revealed that TRPM7 regulated myosin II–based cellular tension, thereby modifying focal adhesion number, cell–cell adhesion, and polarized cell movement.

“The most important discovery that we report in this paper is that TRPM7 is required for metastasis, at least in a xenograft model of breast cancer metastasis,” said contributing author Dr. Frank van Leeuwen, assistant professor of pediatric oncology at Radbound University Medical Center. “While this fundamental biological finding will not have an immediate impact on patient care, we believe that it opens the door to a previously under-explored area of cancer therapeutics.

“TRPM7 functions as a cation channel,” said Dr. van Leeuwen. “As such, it is in a class of proteins that is already therapeutically targeted to treat diseases; for example, cation channel blockers are used to treat several heart conditions. Given that cation channels are druggable; our data provide clear rationale for probing whether drugs that target this class of proteins could block metastasis.”

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Radbound University Medical Center