Research ArticleCancer Biology

TRPS1 Targeting by miR-221/222 Promotes the Epithelial-to-Mesenchymal Transition in Breast Cancer

Sci. Signal.  14 Jun 2011:
Vol. 4, Issue 177, pp. ra41
DOI: 10.1126/scisignal.2001538

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Parsing Breast Cancer Subtype with MicroRNAs

MicroRNAs (miRNAs), short noncoding RNAs that bind to and silence target mRNAs, have emerged as playing crucial regulatory roles not only in normal cellular processes but also in pathological conditions, such as cancer. Stinson et al. analyzed miRNA expression in different types of human breast cancer and found that miR-221 and miR-222 (miR-221/222) abundance was increased in the clinically aggressive basal-like subtype compared to the less aggressive luminal subtype. They determined that signaling through the epidermal growth factor receptor (EGFR)–RAS–extracellular signal–regulated kinase (ERK) pathway increased miR-221/222 transcription, and they defined a transcriptional regulatory pathway through which miR-221/222 promoted a phenotype associated with cancer cell invasion and metastasis. Their data suggest that combining inhibition of the EGFR-RAS-ERK pathway with standard chemotherapy could, by limiting miR-221/222 production, provide a strategy to combat metastasis in the basal-like subtype of breast cancer.