Research ArticleCancer Biology

EGF Decreases the Abundance of MicroRNAs That Restrain Oncogenic Transcription Factors

Sci. Signal.  01 Jun 2010:
Vol. 3, Issue 124, pp. ra43
DOI: 10.1126/scisignal.2000876

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A Loss of Restraint

Growth factors, such as epidermal growth factor (EGF), bind to receptors to stimulate cell proliferation, a process critical during development and in wound healing. Dysregulation of the signaling pathways initiated by the EGF receptor (EGFR) has been implicated in cancer. Noting that aberrant expression of microRNAs, small noncoding RNAs that inhibit the expression of target genes, is common in human malignancies, Avraham et al. explored the role of microRNAs in regulating EGFR signaling. They found that EGF elicited a rapid—and transient—decrease in the abundance of a group of 23 microRNAs, thereby enabling the induction of potentially oncogenic transcription factor targets. Moreover, the abundance of this group of microRNAs was decreased in breast cancers and brain cancers with molecular lesions consistent with increased EGFR signaling. The authors conclude that, under basal conditions, this group of microRNAs restrains potentially oncogenic signaling pathways downstream of the EGFR. Their decreased abundance in cancer thus enables the dysregulated activity of oncogenic transcription factors and signaling pathways transiently activated by EGF signaling, thereby promoting the aberrant cellular behaviors associated with cancer.

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