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PKCθ-induced phosphorylations control the ability of Fra-1 to stimulate gene expression and cancer cell migration.
Belguise, Karine; Cherradi, Sara; Sarr, Awa; Boissière, Florence; Boulle, Nathalie; Simony-Lafontaine, Joëlle; Choesmel-Cadamuro, Valérie; Wang, Xiaobo; Chalbos, Dany.
Afiliação
  • Belguise K; IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, France; INSERM, U1194, Montpellier, F-34298, France; Université de Montpellier, Montpellier, F-34090, France; Institut de Cancérologie de Montpellier, Montpellier, F-34298, France. Electronic address: karine.belguise@u
  • Cherradi S; IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, France; INSERM, U1194, Montpellier, F-34298, France; Université de Montpellier, Montpellier, F-34090, France; Institut de Cancérologie de Montpellier, Montpellier, F-34298, France.
  • Sarr A; IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, France; INSERM, U1194, Montpellier, F-34298, France; Université de Montpellier, Montpellier, F-34090, France; Institut de Cancérologie de Montpellier, Montpellier, F-34298, France.
  • Boissière F; Unité de Recherche Translationnelle, Institut Régional du Cancer de Montpellier, Montpellier, F-34298, France.
  • Boulle N; Département de Biopathologie, CHU Montpellier, Montpellier, F-34295, France.
  • Simony-Lafontaine J; Unité de Recherche Translationnelle, Institut Régional du Cancer de Montpellier, Montpellier, F-34298, France.
  • Choesmel-Cadamuro V; LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31062, Toulouse, France.
  • Wang X; LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31062, Toulouse, France.
  • Chalbos D; IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, France; INSERM, U1194, Montpellier, F-34298, France; Université de Montpellier, Montpellier, F-34090, France; Institut de Cancérologie de Montpellier, Montpellier, F-34298, France. Electronic address: dany.chalbos@inse
Cancer Lett ; 385: 97-107, 2017 01 28.
Article em En | MEDLINE | ID: mdl-27816489
The AP-1 transcription factor Fra-1 is aberrantly expressed in a large number of cancers and plays crucial roles in cancer development and progression by stimulating the expression of genes involved in these processes. However, the control of Fra-1 transactivation ability is still unclear and here we hypothesized that PKCθ-induced phosphorylation could be necessary to obtain a fully active Fra-1 protein. Using MCF7 stable cells overexpressing equivalent levels of unphosphorylated Fra-1 or PKCθ-phosphorylated Fra-1, we showed that PKCθ-induced phosphorylation of Fra-1 was crucial for the stimulation of MMP1 and IL6 expression. Consistently, we found a significant positive correlation between PRKCQ (coding for PKCθ) and MMP1 mRNA expression levels in human breast cancer samples. PKCθ-induced phosphorylations, in part at T217 and T227 residues, strongly and specifically increased Fra-1 transcriptional activity through the stimulation of Fra-1 transactivation domain, without affecting JUN factors. More importantly, these phosphorylations were required for Fra-1-induced migration of breast cancer cells and phosphorylated Fra-1 expression was enriched at the invasion front of human breast tumors. Taken together, our findings indicate that PKCθ-induced phosphorylation could be important for the function of Fra-1 in cancer progression.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Neoplasias da Mama / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Movimento Celular / Proteínas Proto-Oncogênicas c-fos / Isoenzimas Limite: Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteína Quinase C / Neoplasias da Mama / Biomarcadores Tumorais / Regulação Neoplásica da Expressão Gênica / Movimento Celular / Proteínas Proto-Oncogênicas c-fos / Isoenzimas Limite: Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article