Statin May Block Protein Pathway That Promotes Breast Cancer, Study Reports

Statin May Block Protein Pathway That Promotes Breast Cancer, Study Reports
A metabolic pathway that is upregulated in some breast cancers promotes disease progression by activating a specific cell signaling protein called Arf6, a study reported. But the researchers, working in a mouse model, also found that a lipid-lowering drug, simvastatin, inhibited metastasis, suggesting this statin class of medication can be an effective therapeutic approach in Arf6-expressing breast tumors. The study, “P53- and mevalonate pathway–driven malignancies require Arf6 for metastasis and drug resistance,” was recently published in The Journal of Cell Biology. The ADP-ribosylation factor 6 (ARF6) protein has a variety of cellular functions and is often overexpressed in tumors, promoting cell detachment (epithelial–mesenchymal transition) and invasiveness of healthy tissue. Such characteristics, coupled with drug resistance, are the building blocks of aggressive breast tumors. The metabolic mevalonate pathway (MVP), essential for the production of important molecules such as cholesterol and long-chain lipid groups, has also been associated with tumor invasiveness, but the molecular mechanisms behind this effect are unknown. Researchers found that the MVP requires the Arf6 signaling pathway, promoting its recruitment to the plasma membrane, where Arf6 is activated. This process involves the generation of a lipid group that anchors a protein called Rab11b to cell membranes, allowing it to deliver Arf6 to its site of activation. Moreover, a known tumorigenesis promoter, called the mutant p53 protein, promotes Arf6 activation. The team found that inhibiting Rab11b reduced the invasiveness of the MDA-MB-231 breast cancer ce
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