Author(s): Liu, M. ; Banerjee, R. ; Rossa, C. [UNESP] ; D’Silva, N. J.
Date: 2020
Persistent ID: http://hdl.handle.net/11449/200439
Origin: Oasisbr
Subject(s): cal adhesion kinase; extracellular matrix; fibronectin; integrin α5β1; small GTPases; squamous cell carcinoma; cal adhesion kinase; cal adhesion kinase; extracellular matrix; extracellular matrix; fibronectin; fibronectin; integrin α5β1; integrin α5β1; small GTPases; small GTPases; squamous cell carcinoma; squamous cell carcinoma
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
National Institute of Dental and Craniofacial Research
Cell-cell adhesion is a key mechanism to control tissue integrity and migration. In head and neck squamous cell carcinoma (HNSCC), cell migration facilitates distant metastases and is correlated with poor prognosis. RAP1, a ras-like protein, has an important role in the progression of HNSCC. RAC1 is an integrin-linked, ras-like protein that promotes cell migration. Here we show that loss of cell-cell adhesion is correlated with inactivation of RAP1 confirmed by 2 different biochemical approaches. RAP1 activation is required for cell-matrix adhesion confirmed by adhesion to fibronectin-coated plates with cells that have biochemically activated RAP1. This effect is reversed when RAP1 is inactivated. In addition, RAP1GTP-mediated adhesion is only facilitated through α5β1 integrin complex and is not a function of either α5 or β1 integrin alone. Moreover, the inside-out signaling of RAP1 activation is coordinated with RAC1 activation. These findings show that RAP1 has a prominent role in cell-matrix adhesion via extracellular matrix molecule fibronectin-induced α5β1 integrin and supports a critical role for the RAP1/RAC1 signaling axis in HNSCC cell migration.
Department of Periodontics and Oral Medicine University of Michigan School of Dentistry
Department of Diagnosis and Surgery School of Dentistry at Araraquara UNESP—Univ Estadual Paulista
Department of Pathology Medical School University of Michigan
Department of Diagnosis and Surgery School of Dentistry at Araraquara UNESP—Univ Estadual Paulista
FAPESP: 2014/50312-4
FAPESP: 2017/14283-5
National Institute of Dental and Craniofacial Research: DE022567
National Institute of Dental and Craniofacial Research: DE027551
