Correction: The anti-metastatic activity of collagenase-2 in breast cancer cells is mediated by a signaling pathway involving decorin and miR-21.

The original microRNA hybridization data for this article, which has been available for the scientific community upon request, has now been deposited in the GEO repository under accession number GSE124432.

NF-κB signaling as a driver of ageing.

NF-κB signaling exerts essential roles in immunity and cellular stress responses, regulating many functions related with organism innate defense. Besides, NF-κB altered signaling has been causally linked to ageing and diverse pathological conditions. We discuss herein the functional involvement of this signaling pathway in ageing, visiting recent experimental evidence about NF-κB activation in this complex process, its functional consequences and the novel biological functions raised from these works. Moreover, we discuss ageing intervention strategies based on NF-κB inhibition, which have demonstrated to be effective at delaying and even reverting different ageing manifestations in human and mouse models of both normal and accelerated ageing. Altogether, the current evidence supports that NF-κB activation constitutes a driving force of the ageing process and a preferential target for rejuvenation-aimed approaches.

The anti-metastatic activity of collagenase-2 in breast cancer cells is mediated by a signaling pathway involving decorin and miR-21.

Matrix metalloproteinases (MMPs) have been traditionally implicated in cancer progression because of their ability to degrade the extracellular matrix. However, some members of the MMP family have recently been identified as proteases with antitumor properties. Thus, it has been described that collagenase-2 (MMP-8) has a protective role in tumor and metastasis progression, but the molecular mechanisms underlying these effects are unknown. We show herein that Mmp8 expression causes a decrease in miR-21 levels that in turn leads to a reduction in tumor growth and lung metastasis formation by MDA-MB-231 (4175) breast cancer cells. By using both in vitro and in vivo models, we demonstrate that the mechanism responsible for these MMP-8 beneficial effects involves cleavage of decorin by MMP-8 and a subsequent reduction of transforming growth factor ß (TGF-ß) signaling that controls miR-21 levels. In addition, miR-21 downregulation induced by MMP-8 increases the levels of tumor suppressors such as programmed cell death 4, which may also contribute to the decrease in tumor formation and metastasis of breast cancer cells overexpressing this metalloproteinase. These findings reveal a new signaling pathway for cancer regulation controlled by MMP-8, and contribute to clarify the molecular mechanisms by which tumor-defying proteases may exert their protective function in cancer and metastasis.