P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer

The GTPase Rac1 is a well-established master regulator of cell motility and invasiveness contributing to cancer metastasis. Dysregulation of the Rac1 signaling pathway, resulting in elevated motile and invasive potential, has been reported in multiple cancers. However, there are limited studies on t...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Baker, Martin J., Abba, Martín Carlos, Garcia-Mata, Rafael, Kazanietz, Marcelo G.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/107862
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7072377&blobtype=pdf
Aporte de:
id I19-R120-10915-107862
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Médicas
Rac1
P-Rex1
Rac-GEF
Calcium
Prostate cancer cells
spellingShingle Biología
Ciencias Médicas
Rac1
P-Rex1
Rac-GEF
Calcium
Prostate cancer cells
Baker, Martin J.
Abba, Martín Carlos
Garcia-Mata, Rafael
Kazanietz, Marcelo G.
P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer
topic_facet Biología
Ciencias Médicas
Rac1
P-Rex1
Rac-GEF
Calcium
Prostate cancer cells
description The GTPase Rac1 is a well-established master regulator of cell motility and invasiveness contributing to cancer metastasis. Dysregulation of the Rac1 signaling pathway, resulting in elevated motile and invasive potential, has been reported in multiple cancers. However, there are limited studies on the regulation of Rac1 in prostate cancer. Here, we demonstrate that aggressive androgen-independent prostate cancer cells display marked hyperactivation of Rac1. This hyperactivation is independent of P-Rex1 activity or its direct activators, the PI3K product PIP3 and Gβγ subunits. Furthermore, we demonstrate that the motility and invasiveness of PC3 prostate cancer cells is independent of P-Rex1, supporting the analysis of publicly available datasets indicating no correlation between high P-Rex1 expression and cancer progression in patients. Rac1 hyperactivation was not related to the presence of activating Rac1 mutations and was insensitive to overexpression of a Rac-GAP or the silencing of specific Rac-GEFs expressed in prostate cancer cells. Interestingly, active Rac1 levels in these cells were markedly reduced by elevations in intracellular calcium or by serum stimulation, suggesting the presence of an alternative means of Rac1 regulation in prostate cancer that does not involve previously established paradigms.
format Articulo
Articulo
author Baker, Martin J.
Abba, Martín Carlos
Garcia-Mata, Rafael
Kazanietz, Marcelo G.
author_facet Baker, Martin J.
Abba, Martín Carlos
Garcia-Mata, Rafael
Kazanietz, Marcelo G.
author_sort Baker, Martin J.
title P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer
title_short P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer
title_full P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer
title_fullStr P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer
title_full_unstemmed P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer
title_sort p-rex1-independent, calcium-dependent rac1 hyperactivation in prostate cancer
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/107862
http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7072377&blobtype=pdf
work_keys_str_mv AT bakermartinj prex1independentcalciumdependentrac1hyperactivationinprostatecancer
AT abbamartincarlos prex1independentcalciumdependentrac1hyperactivationinprostatecancer
AT garciamatarafael prex1independentcalciumdependentrac1hyperactivationinprostatecancer
AT kazanietzmarcelog prex1independentcalciumdependentrac1hyperactivationinprostatecancer
bdutipo_str Repositorios
_version_ 1764820443715338241