Rôle du facteur de réparation de l'ADN KU dans les interactions cellules/matrice extracellulaire

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

The double life of the Ku protein: facing the DNA breaks and the extracellular environment.

The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double strand break recognition and repair. It has been shown, more than ten years ago, that Ku is also expressed at the cell surface of different cells types along with its intracellular pool within the nucleus and the cytoplasm but involvement of Ku in cell-cell and cell-extracellular matrix adhesion has been only recently demonstrated. In addition, we have shown that Ku may have a second and unexpected activity in cell/microenvironment interaction. Indeed, Ku appears to be involved in extracellular proteolytic processes through its specific interaction, on the cell surface, with the matrix metalloprotease 9. Taken together, these results suggest that Ku function at the cell surface is likely to be important in tumour invasion. Various fundamental questions arise from these observations. How Ku is expressed on the cell surface, why a protein with completely unrelated functions also serve as an integrin-like molecule once expressed at the cell surface and is this functional moonlighting of Ku related to cell transformation remain open issues that will be discussed here

Endogenous Mobilization of Mesenchymal Stromal Cells: A Pathway for Interorgan Communication?

International audienceTo coordinate specialized organs, inter-tissue communication appeared during evolution. Consequently, individual organs communicate their states via a vast interorgan communication network (ICN) made up of peptides, proteins, and metabolites that act between organs to coordinate cellular processes under homeostasis and stress. However, the nature of the interorgan signaling could be even more complex and involve mobilization mechanisms of unconventional cells that are still poorly described. Mesenchymal stem/stromal cells (MSCs) virtually reside in all tissues, though the biggest reservoir discovered so far is adipose tissue where they are named adipose stromal cells (ASCs). MSCs are thought to participate in tissue maintenance and repair since the administration of exogenous MSCs is well known to exert beneficial effects under several pathological conditions. However, the role of endogenous MSCs is barely understood. Though largely debated, the presence of circulating endogenous MSCs has been reported in multiple pathophysiological conditions, but the significance of such cell circulation is not known and therapeutically untapped. In this review, we discuss current knowledge on the circulation of native MSCs, and we highlight recent findings describing MSCs as putative key components of the ICN

Gq-coupled Purinergic Receptors Inhibit Insulin-like Growth Factor-I/Phosphoinositide 3-Kinase Pathway-dependent Keratinocyte Migration

After skin wound, released growth factors and extracellular nucleotides regulate the different phases of healing, including re-epithelialization. Here, we show that, in keratinocytes, purinergic P2Y2 receptors inhibit the motogenic IGF-I/PI3K pathway. Therefore, extracellular nucleotides may play key roles during skin remodelling after wound

The RND1 Small GTPase: Main Functions and Emerging Role in Oncogenesis

The Rho GTPase family can be classified into classic and atypical members. Classic members cycle between an inactive Guanosine DiPhosphate -bound state and an active Guanosine TriPhosphate-bound state. Atypical Rho GTPases, such as RND1, are predominantly in an active GTP-bound conformation. The role of classic members in oncogenesis has been the subject of numerous studies, while that of atypical members has been less explored. Besides the roles of RND1 in healthy tissues, recent data suggest that RND1 is involved in oncogenesis and response to cancer therapeutics. Here, we present the current knowledge on RND1 expression, subcellular localization, and functions in healthy tissues. Then, we review data showing that RND1 expression is dysregulated in tumors, the molecular mechanisms involved in this deregulation, and the role of RND1 in oncogenesis. For several aggressive tumors, RND1 presents the features of a tumor suppressor gene. In these tumors, low expression of RND1 is associated with a bad prognosis for the patients. Finally, we highlight that RND1 expression is induced by anticancer agents and modulates their response. Of note, RND1 mRNA levels in tumors could be used as a predictive marker of both patient prognosis and response to anticancer agents