Recent work from Dey et al. showed that miR-21 targets PTEN protein expression and promotes ccRCC survival and invasion through Akt/TORC1 signaling [52]. Taken together, our data provide strong evidence that Hippo signaling plays an important role in regulating proliferation, invasiveness, and metastatic potential of ccRCC and might serve as a target for therapeutic intervention in the future. Disrupted Hippo signaling and consecutive derepression and activation of YAP lead to increased production of the putative YAP target genes EDN1, EDN2, and c-Myc. Increased endothelin signaling in turn results in increased production CDK inhibition of proproliferative and proinvasive mediators by ccRCC cells and

might thus enhance metastatic colonization. Therefore, future studies aimed at developing specific inhibitory drugs of the Hippo signaling pathway or its downstream effectors described here seem warranted to generate novel therapeutic regimens against ccRCC.

We thank Miriam Menger, Nadine Fricker, and Martin Mahlberg for excellent technical assistance. The authors disclose no potential conflicts of interest. “
“Murine 12/15-lipoxygenase (LOX) and its human homolog 15-LOX have long been known as generators of free acid eicosanoids, primarily 12- and 15-hydroxyeicosatetraenoic acids (HETEs), respectively. More recently, we showed these enzymes directly oxidize intact phospholipid, generating phosphatidylethanolamine (PE)-esterified forms that can dampen Toll-like receptor 4 signaling in human monocytes [1] and [2]. Analogous

lipids are generated by neutrophil 5-LOX and platelet 12-LOX, including MK 2206 phosphatidylcholine (PC) esterified homologs that can stimulate coagulation and regulate leukocyte anti-bacterial actions [3] and [4]. Since HETE-PEs remain cell associated following their generation, we sought to examine whether they could be involved in membrane regulatory processes. Autophagy is the process by which cells remove ageing organelles and damaged cellular structures [5]. There are three defined types of autophagy: macro-, micro-, and chaperone-mediated, all of which promote proteolytic degradation of cytosolic components at the lysosome. Autophagy begins with Idelalisib an isolation membrane, also known as a phagophore that is likely derived from lipid bilayer contributed by the endoplasmic reticulum (ER) and/or the trans-Golgi and endosomes. This expands to engulf intracellular cargo, sequestering it in a double-membraned autophagosome. This matures through lysosome fusion, promoting degradation of autophagosomal contents by lysosomal hydrolases. Lysosomal permeases and transporters export amino acids and other by-products of degradation back out to the cytoplasm, where they are re-used for cellular processes [6]. One particular type of autophagy, mitophagy, which removes old and damaged mitochondria, comprises several different processes termed Types 1–3 [7].