LRP-1 Promotes Cancer Cell Invasion by Supporting ERK and Inhibiting JNK Signaling Pathways

Background: The low-density lipoprotein receptor-related protein-1 (LRP-1) is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated. The lack of mechanistic insights into the intracellular signaling networks downstream of LRP-1 has prevented the understanding of its contribution towards cancer. Methodology/Principal Findings: Through a short-hairpin RNA-mediated silencing approach, we identified LRP-1 as a main regulator of ERK and JNK signaling in a tumor cell context. Co-immunoprecipitation experiments revealed that LRP-1 constitutes an intracellular docking site for MAPK containing complexes. By using pharmacological agents, constitutively active and dominant-negative kinases, we demonstrated that LRP-1 maintains malignant cells in an adhesive state that is favorable for invasion by activating ERK and inhibiting JNK. We further demonstrated that the LRP-1-dependent regulation of MAPK signaling organizes the cytoskeletal architecture and mediates adhesive complex turnover in cancer cells. Moreover, we found that LRP-1 is tethered to the actin network and to focal adhesion sites and controls ERK and JNK targeting to talin-rich structures. Conclusions: We identified ERK and JNK as the main molecular relays by which LRP-1 regulates focal adhesion disassembly of malignant cells to support invasion

The relationship between rifting and magmatism in the northeastern Arabian Sea

The causal mechanisms linking continental flood basalts, lithospheric extension and mantle plumes, as well as the relative timing of extension and volcanism, are controversial1, 2, 3, 4. The eruption of the Deccan flood basalts was approximately contemporaneous with the separation of the Seychelles microcontinent from India. However, between these continental blocks lies the enigmatic Laxmi Ridge, and the sequence of extensional events that formed these various tectonic elements is poorly understood. Here we present wide-angle seismic data along a profile across Laxmi Ridge that permit delineation of offshore igneous bodies associated with the Deccan magmatism; these bodies are similar to those associated with flood-basalt volcanism and rifting in the Atlantic region and elsewhere1. From the geometry of these bodies, we infer that there were two periods of extension. The first phase, which involved extension between Laxmi Ridge and the Indian subcontinent, was accompanied by significant Deccan-related magmatism. Full development of a continental margin was achieved during the second phase of weakly magmatic extension between Laxmi Ridge and the Seychelles. We suggest that between these rifting events the region passed beyond the reach of lateral flow from the source region of the Deccan flood basalts

The appeasement effect of a United Nations climate summit on the German public

The annual UN climate summits receive intense global media coverage(1-3), and as such could engage local publics around the world, stimulate debate and knowledge about climate politics, and, ultimately, mobilize people to combat climate change. Herewe showthat, in contrast to these hopes, although the German public were exposed to news about the 2015 Paris summit, they did not engage with it in a more active way. Comparing knowledge and attitudes before, during and after the summit using a three-wave online panel survey (quota sample, N = 1,121), we find that respondents learnt a few basic facts about the conference but they continue to lack basic background knowledge about climate policy. Trust in global climate policy increased a little, but citizens were less inclined to support a leading role for Germany in climate politics. Moreover, they were not more likely to engage personally in climate protection. These results suggest that this global media event had a modest appeasing rather than mobilizing effect