A paper from Taverna’s group presents a novel pathway, critical for melanoma dissemination, involving miR-214, miR-148b, TFAP2 and ALCAM. By using a human melanoma model, Taverna’s group previously demonstrated that miR-214 coordinates melanoma invasion, extravasation and metastasis dissemination and identified TFAP2 transcription factors as miR-214’s direct targets. Now, Penna et al. show that miR-214 also drives the upregulation of a cell-to-cell adhesion molecule, ALCAM via TFAP2, directly by repressing ALCAM transcription and indirectly by controlling miR-148b, a small non-coding RNA able to target ALCAM. In the paper, a key role for ALCAM in miR-214-mediated pro-metastatic functions is highlighted. Overall, the data indicate that miR-214 and miR-148b and their targets TFAP2 and ALCAM, are part of a novel regulatory loop which controls melanoma malignancy that could be used for therapeutic interventions.
A paper by Arigoni and collegues published on American Journal of Pathology shows that miR-135b coordinates progression of ErbB2-driven mammary carcinomas through suppression of MID1 and MTCH2 genes. In this work, the authors find increased expression of miR-135b during mammary malignancy of BALB/c mice transgenic for the rat-ErbB-2 oncogene (BALB-neuT), observed that it is up-regulated in basal or normal-like human breast cancers and that its up-regulation correlates with patient survival and early metastatization. Moreover, they show that miR-135b is involved in the control of cancer cell stemness in a mammosphere assay, anchorage-independent growth in vitro and lung cancer cell dissemination in mice following tail vein injections. Focusing on miR-135b molecular mechanism, they observed that miR-135b controls malignancy via its direct targets MID1 and MTCH2 as proven by biochemical and functional rescuing/phenocopying experiments. In line with this, an anti-correlation between miR-135b and MID1 or MTCH2 was found in human primary tumor samples. In conclusion, this research led the authors to the identification of miR-135b and its targets MID1 and MTCH2 as relevant coordinators of mammary gland tumor progression.
A paper from Cabodi’s group describes that the adaptor protein p130Cas is a crucial regulator of mouse mammary epithelial cell (MMEC) differentiation. By using a transgenic mouse model, Tornillo et al., show that forced p130Cas over-expression in the luminal progenitor cell compartment results in the expansion of luminal cells, which aberrantly display basal cell features and reduced differentiation in response to lactogenic stimuli. Interestingly, MMECs over-expressing p130Cas exhibit hyperactivation of the tyrosine kinase receptor c-Kit and the constitutive c-Kit activation alone mimics p130Cas over-expression whereas c-Kit downregulation is sufficient to re-establish proper differentiation of p130Cas over-expressing cells. Overall, these data indicate that high levels of p130Cas, via abnormal c-Kit activation, promote mammary luminal cell plasticity, thus providing the conditions for the development of basal-like breast cancer. Consistently, p130Cas is over-expressed in human triple negative breast cancer, further suggesting that p130Cas upregulation may be a priming event for the onset of basal-like breast cancer.
S EM I NA R I O Vieni a prendere un caffè da noi e scoprirai tutte le novità VWR PBI
23 maggio dalle ore 9 alle 15 giardino interno MBC
Prof. Stephan Geley
Biocenter of Innsbruck Medical University
Functional analysis of fizzy/cell division cycle 20 related 1 (FZR1) in vertebrates.
Giovedì, 23 Maggio 2013, ore 14.00
MBC, Via Nizza 52, aula Seminari
Ospite: Ferdinando Di Cunto
Prof Stefano Gustincich (SISSA, Trieste)
venerdì 24 maggio ore 13:00 in Aula Seminari
SINEUPs a new functional class of natural and synthetic antisense long non - coding RNAs that activate translation