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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC

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Author(s):
Liu, M. [1] ; Banerjee, R. [1] ; Rossa Jr, C. ; D'Silva, N. J. [2, 3]
Total Authors: 4
Affiliation:
[1] Univ Michigan, Dept Periodont & Oral Med, Sch Dent, 1011 North Univ Ave, Room G018, Ann Arbor, MI 48109 - USA
[2] Univ Michigan, Dept Pathol, Med Sch, Ann Arbor, MI 48109 - USA
[3] 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
Document type: Journal article
Source: JOURNAL OF DENTAL RESEARCH; v. 99, n. 8 MAY 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 17/14283-5 - Cross-talk between cancer and immune cells in oral squamous cell carcinoma invasion and metastasis: study in a novel in vivo model
Grantee:Carlos Rossa Junior
Support Opportunities: Scholarships abroad - Research