PHILADELPHIA The protein transient receptor potential melastatin-like 7 (TRPM7) is a critical determinant of breast cancer cell metastasis, according to study results published in Cancer Research, a journal of the American Association for Cancer Research.
"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 Frank van Leeuwen, Ph.D., assistant professor at the Radbound University Medical Center in Nijmegen, the Netherlands. "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. 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."
Central to tumor metastasis are changes in the capacity of tumor cells to adhere to other cells and tissue at the original tumor site and changes in their ability to migrate. As TRPM7 was known to be involved in regulating cell adhesion and migration, van Leeuwen and his colleagues, including researchers at The Netherlands Cancer Institute in Amsterdam, set out to investigate whether TRMP7 had a role in cancer cell metastasis.
They evaluated whether the level of expression of the TRPM7 gene correlated with breast cancer progression. 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 bre
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American Association for Cancer Research