The roles of integrin β₄ in Vascular Endothelial Cells

Abstract

Integrin heterodimers play diverse and important roles in physiological and pathological processes, such as cell adhesion, migration, proliferation, differentiation, angiogenesis, and tumor progression, via the outside-in and/or inside-out signaling pathways. Aberrant functions of integrins have been implicated in the causation and intervention of multiple diseases. Integrin β(4), a laminin-5 (LN5) receptor, mainly locates in the adhesion structure of hemidesmosome (HD). Most of the previous researches concentrated on the role of integrin β(4) in cancer and cancer therapy, and a few focused on the physiological roles of normal mammalian cells. Recently, accumulating data reveal that integrin β(4) participates in cell death, macroautophagy (hereafter autophagy), senescence, and differentiation regulations in various cell types including human umbilical vein endothelial cells (HUVECs), mesenchymal stem cells, and mouse neural cells, implying the key roles of integrin β(4) in the physiological alteration of mammalian cells. Thus, the elucidation of integrin β(4)-mediated signaling may undoubtedly contribute to novel therapeutic strategies for various human diseases, such as vascular and neural disorders. We have reviewed the roles of integrin β(4) in neural cells. In the present review we will discuss the recent research progress in the inherent functions and pharmacological modulation of integrin β(4) in vascular endothelial cells.

Integrin β4 promotes cell invasion and epithelial-mesenchymal transition through the modulation of Slug expression in hepatocellular carcinoma

“…Integrins are heterodimers composed of an α and a β subunit, and they play important roles in many physiological and pathological processes, including cell adhesion, migration, proliferation, differentiation, and tumor progression6. Integrin β4 (ITGB4) is a laminin-5 receptor that is predominantly expressed in squamous epithelial cells, endothelial cells, immature thymocytes, Schwann cells, and fibroblasts of the peripheral nervous system7. The ITGB4 subunit, which is characterized by its particularly long cytoplasmic signaling domain, pairs only with the α6 subunit, and the heterodimeric integrin α6β4 plays a role in the invasive and metastatic phenotype of various cancers89.…”

Clinical significance of the integrin α6β4 in human malignancies

“…In addition to promoting invasive properties in carcinoma cells, the integrin α6β4 can stimulate invasion and migration of endothelial cells, processes that are necessary for pathologic angiogenesis (5) (for review, see (77, 78)). Studies using knockout mice carrying a deletion in the signaling domain of the integrin β4 subunit displayed reduced angiogenesis in a retinal neovascularization model, and developed smaller and less vascularized tumors after subcutaneous implantation (5).…”

The role of endoglin in post-ischemic revascularization

“…Furthermore, CXCL12-induced expression of PDGF-B is in turn a potent activator of integrins [63]. However, despite the emerging relevant role of integrins as cell adhesion receptors in vascular biology [64][65][66], their involvement in the interaction between ECs and mural cells remains largely unexplored.…”