Researchers at the GRU Cancer Center have identified new molecular players and potential biomarkers in breast cancer tumorigenesis. A process known as epithelial-to-mesenchymal transition (EMT) represents changes in cancer cell characteristics that accompany metastatic progression. Epithelial-like cancer cells express different molecular constituents than do mesenchymal-like cells.
Dr. Shuang Huang and colleagues have previously reported that three noncoding RNAS (microRNAs, or miRNAs), which are molecules that can affect gene expression, are predominantly associated with epithelial-like breast cancer cells. Two of these miRNAs are known to suppress EMT, and the Huang group now reports in Neoplasia, that the third, miR-375, does as well. They went on to show that miR-375 suppresses EMT by undermining the expression of the SHOX2 protein, which is typically expressed in mesenchymal-like versus epithelial-like breast cancer cells. Their data demonstrate that depletion of SHOX2 blocks experimental models of metastasis, both in vitro and in vivo. Conversely, induced SHOX2 expression in epithelial-like breast cancer cells promoted metastasis in these models. Further studies linked the SHOX2 induction of metastasis to TGFb signaling in breast cancer cells. Referencing human breast tumor microarray data, they also report that low SHOX2 expression corresponded to increased survival. Overall, this research reveals a regulatory relationship between miR-375 and SHOX2 that controls EMT and breast tumorigenesis, potentially through TGFb signaling.[Hong S, Noh H, Teng Y, Shao J, Rehmani H, Ding HF, Dong Z, Su SB, Shi H, Kim J, Huang S. SHOX2 Is a Direct miR-375 Target and a Novel Epithelial-to-Mesenchymal Transition Inducer in Breast Cancer Cells. Neoplasia. 2014 Apr 16. pii: S1476-5586(14)00029-3. doi: 10.1016/j.neo.2014.03.010. [Epub ahead of print]]