Integrin‐dependent pathologies

Abstract

Cell adhesion and migration are essential for embryonic development, tissue regeneration, and immune defence. The physical link between the extracellular substrate and the actin cytoskeleton is mediated by receptors of the integrin family and a large set of adaptor proteins. During cell migration this physical link is dynamically modified, allowing the cell to sense and adapt to the microenvironment. This includes the formation of integrin clusters at the cell front, their stabilization in the cell body and subsequent disassembly of these clusters at the rear of the cell. The modulation of the adhesion strength of the cell to the substrate is regulated by the affinity switch of integrin molecules and increased avidity through clustering of integrins. Here we explain how integrins mediate cell migration and how genetic defects of integrins and their adaptors lead to cellular dysfunction and generate pathological situations.

Collagen-Dependent Neurite Outgrowth and Response to Dynamic Deformation in Three-Dimensional Neuronal Cultures

“…33,58 However, the role of cell-ECM adhesions in acute and chronic responses following traumatic neural loading is currently not known. In many non-neural systems, cells communicate with their immediate physical environment through such interactions and alter intracellular biochemical signaling in response to mechanical cues, a process referred to as mechanotransduction.…”

Increased adenoviral transduction efficacy in human laryngeal carcinoma cells resistant to cisplatin is associated with increased expression of integrin αvβ3 and coxsackie adenovirus receptor

“…Integrins can affect many diverse aspects of cell behavior, thus having important role in tissue development, function and disease. 20,21 Drug-resistance of tumor cells is the major obstacle for successful treatment of cancer patients. Different molecular mechanisms have been recognized as the cause of resistance among which the most common are reduced intracellular drug accumulation due to the inactivation of ATP-binding cassette transporters, increased drug inactivation by the intracellular detoxification system, increased ability of cells to repair and/or tolerate DNA lesions, altered activity of nuclear enzymes and inhibition of apoptosis.…”

L’intégrine αIIbβ3

“…Lorsque le phénomène d'endomitose s'arrête, une maturation cytoplasmique est alors observée avec le développement de membranes de démarcation (correspondant à des invaginations de la membrane plasmique) et la formation de nombreux granules. giques, tels que la réponse immunitaire, l'hémostase, l'angiogenèse, ou les néoplasies [11][12][13]. L'inté grine α IIb β 3 appartient à la sous-famille des inté-grines β 3 qui englobe également l'α V β 3 , qui est le récep-teur de la vitronectine 5 .…”