Rossa Jr, C.
D'Silva, N. J.
Total Authors: 4
 Univ Michigan, Dept Periodont & Oral Med, Sch Dent, 1011 North Univ Ave, Room G018, Ann Arbor, MI 48109 - USA
 Univ Michigan, Dept Pathol, Med Sch, Ann Arbor, MI 48109 - USA
 Rossa Jr, Jr., C., Univ Michigan, Dept Periodont & Oral Med, Sch Dent, 1011 North Univ Ave, Room G018, Ann Arbor, MI 48109 - USA
Total Affiliations: 3
JOURNAL OF DENTAL RESEARCH;
Web of Science Citations:
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, RAP1(GTP)-mediated adhesion is only facilitated through alpha 5 beta 1 integrin complex and is not a function of either alpha 5 or beta 1 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 alpha 5 beta 1 integrin and supports a critical role for the RAP1/RAC1 signaling axis in HNSCC cell migration. (AU)