TRPA1- FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

YesRecent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD) where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline rich motif. Here, we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2 hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.Faculty of Biological Sciences at the University of Leeds, Wellcome Trust Seed Award, Royal Society Research Grant RG150100, MR/K021303/1, Swedish Research Council (2014-3801) and the Medical Faculty at Lund University

Modélisation théorique et numérique du transport électronique dans les nanostructures

L'objectif de cette thèse dans le domaine de la nanoélectronique est de contribuer à l'analyse des phénomènes de transport électronique quantique dans les nanostructures. Nous développons ainsi spécifiquement la théorie de raccordement des champs de phase (PFMT). Cette approche algébrique décrit les propriétés électroniques du système par les liaisons fortes, mais repose fondamentalement sur la technique de raccordement de phase des états électroniques des électrodes avec ceux sur les nanojonctions moléculaires. En comparant certains de nos résultats avec ceux des méthodes de principes premiers, nous avons montré la justesse et fonctionnalité de notre approche. Une alternative pratique et générale aux nombreuses techniques basées sur la fonction de Green, elle est appliquée dans ce travail de thèse pour modéliser le transport électronique à travers de nanojonctions sous forme de fils mono et diatomiques, constitués d'éléments de Na, Cu, Co, C, Si, Ga et As, mono et multivalents.The aim of this thesis in the nanoelectronics domain is to present a contribution to the analysis of the quantum electronic transport phenomena in nanostructures. For this purpose, we specifically develop the phase field matching theory (PFMT). Within this algebraic approach the electronic properties of the system are described by the tight-binding formalism, whereas the analysis of the transport properties based on the phase matching of the electronic states of the leads to the states of the molecular nanojunctions. By comparing some of our results with those of the first principles methods, we have shown the correctness and fonctionality of our approach. Moreover, our method can be considered as a practical and general alternative to the Green s function-based techniques, and is applied in this work to model the electronic transport across mono and diatomic nanojunctions, consisting of mono and multivalent Na, Cu, Co, C, Si, Ga and As elements.LE MANS-BU Sciences (721812109) / SudocSudocFranceF