RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1177/0022034520917058 http://hdl.handle.net/11449/200439 |
Resumo: | 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. |
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RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCCcal adhesion kinaseextracellular matrixfibronectinintegrin α5β1small GTPasessquamous cell carcinomaCell-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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Institute of Dental and Craniofacial ResearchDepartment of Periodontics and Oral Medicine University of Michigan School of DentistryDepartment of Diagnosis and Surgery School of Dentistry at Araraquara UNESP—Univ Estadual PaulistaDepartment of Pathology Medical School University of MichiganDepartment of Diagnosis and Surgery School of Dentistry at Araraquara UNESP—Univ Estadual PaulistaFAPESP: 2014/50312-4FAPESP: 2017/14283-5National Institute of Dental and Craniofacial Research: DE022567National Institute of Dental and Craniofacial Research: DE027551University of Michigan School of DentistryUniversidade Estadual Paulista (Unesp)University of MichiganLiu, M.Banerjee, R.Rossa, C. [UNESP]D’Silva, N. J.2020-12-12T02:06:43Z2020-12-12T02:06:43Z2020-07-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article959-968http://dx.doi.org/10.1177/0022034520917058Journal of Dental Research, v. 99, n. 8, p. 959-968, 2020.1544-05910022-0345http://hdl.handle.net/11449/20043910.1177/00220345209170582-s2.0-85084994928Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Dental Researchinfo:eu-repo/semantics/openAccess2021-10-23T12:40:01Zoai:repositorio.unesp.br:11449/200439Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T13:55:55.652752Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC |
title |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC |
spellingShingle |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC Liu, M. cal adhesion kinase extracellular matrix fibronectin integrin α5β1 small GTPases squamous cell carcinoma |
title_short |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC |
title_full |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC |
title_fullStr |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC |
title_full_unstemmed |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC |
title_sort |
RAP1-RAC1 Signaling Has an Important Role in Adhesion and Migration in HNSCC |
author |
Liu, M. |
author_facet |
Liu, M. Banerjee, R. Rossa, C. [UNESP] D’Silva, N. J. |
author_role |
author |
author2 |
Banerjee, R. Rossa, C. [UNESP] D’Silva, N. J. |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
University of Michigan School of Dentistry Universidade Estadual Paulista (Unesp) University of Michigan |
dc.contributor.author.fl_str_mv |
Liu, M. Banerjee, R. Rossa, C. [UNESP] D’Silva, N. J. |
dc.subject.por.fl_str_mv |
cal adhesion kinase extracellular matrix fibronectin integrin α5β1 small GTPases squamous cell carcinoma |
topic |
cal adhesion kinase extracellular matrix fibronectin integrin α5β1 small GTPases squamous cell carcinoma |
description |
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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:06:43Z 2020-12-12T02:06:43Z 2020-07-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1177/0022034520917058 Journal of Dental Research, v. 99, n. 8, p. 959-968, 2020. 1544-0591 0022-0345 http://hdl.handle.net/11449/200439 10.1177/0022034520917058 2-s2.0-85084994928 |
url |
http://dx.doi.org/10.1177/0022034520917058 http://hdl.handle.net/11449/200439 |
identifier_str_mv |
Journal of Dental Research, v. 99, n. 8, p. 959-968, 2020. 1544-0591 0022-0345 10.1177/0022034520917058 2-s2.0-85084994928 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Dental Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
959-968 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808128291416047616 |