City of Hope researchers may have identified a substance that contributes to metastasis in breast cancer: microRNAs, particularly one called miR-105 that is secreted by breast cancer cells. The findings were published recently in the journal Cancer Cell.
MicroRNAs are small snippets of genetic code that regulate gene expression. This, in turn, alters the quantity and quality of proteins that are manufactured by those genes. In the study, senior author Emily S. Wang, PhD, and her team found that miR-105 helps breast cancer metastasize by interacting with the gene TJP1. This gene is responsible for producing a protein, ZO-1, used in the boundaries between blood vessel cells.
These boundaries, called tight junctions, are normally impermeable to most substances, including cancer cells. miR-105's interference leads to the degradation of ZO-1, which makes the junction leaky and allows cancer cells to break free from the primary tumor and enter the bloodstream. miR-105's ability to break down tight junctions also helps breast cancer cells invade other organs, including the brain. There, miR-105 leads to the degradation of the blood-brain barrier, which also uses ZO-1.
From these findings as well as animal studies, the researchers suggest that miR-105, which is detectable in the bloodstream, could be used as a biomarker to determine the metastatic potential of a primary breast cancer. It could also be used to catch the beginning of metastasis, giving oncologists enough time to try other treatments before secondary tumors form. Wang and her team are conducting additional preclinical studies on miR-105 and other cancer-secreted microRNAs, with the goals of developing a reliable test to screen for these molecules and drugs that can target them. Read the study.
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