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Peritoneal and hematogenous metastases of ovarian cancer cells are both controlled by the p90RSK through a self-reinforcing cell autonomous mechanism.
Torchiaro, Erica; Lorenzato, Annalisa; Olivero, Martina; Valdembri, Donatella; Gagliardi, Paolo Armando; Gai, Marta; Erriquez, Jessica; Serini, Guido; Di Renzo, Maria Flavia.
Afiliación
  • Torchiaro E; Department of Oncology, University of Torino School of Medicine, Turin, Italy.
  • Lorenzato A; Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia (FPO)-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Italy.
  • Olivero M; Department of Oncology, University of Torino School of Medicine, Turin, Italy.
  • Valdembri D; Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia (FPO)-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Italy.
  • Gagliardi PA; Department of Oncology, University of Torino School of Medicine, Turin, Italy.
  • Gai M; Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia (FPO)-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Italy.
  • Erriquez J; Department of Oncology, University of Torino School of Medicine, Turin, Italy.
  • Serini G; Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia (FPO)-Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Italy.
  • Di Renzo MF; Department of Oncology, University of Torino School of Medicine, Turin, Italy.
Oncotarget ; 7(1): 712-28, 2016 Jan 05.
Article en En | MEDLINE | ID: mdl-26625210
The molecular mechanisms orchestrating peritoneal and hematogenous metastases of ovarian cancer cells are assumed to be distinct. We studied the p90RSK family of serine/threonine kinases that lie downstream the RAS-ERK/MAPK pathway and modulate a variety of cellular processes including cell proliferation, survival, motility and invasiveness. We found the RSK1 and RSK2 isoforms expressed in a number of human ovarian cancer cell lines, where they played redundant roles in sustaining in vitro motility and invasiveness. In vivo, silencing of both RSK1 and RSK2 almost abrogated short-term and long-term metastatic engraftment of ovarian cancer cells in the peritoneum. In addition, RSK1/RSK2 silenced cells failed to colonize the lungs after intravenous injection and to form hematogenous metastasis from subcutaneous xenografts. RSK1/RSK2 suppression resulted in lessened ovarian cancer cell spreading on endogenous fibronectin (FN). Mechanistically, RSK1/RSK2 knockdown diminished FN transcription, α5ß1 integrin activation and TGF-ß1 translation. Reduced endogenous FN deposition and TGF-ß1 secretion depended on the lack of activating phosphorylation of the transcription/translation factor YB-1 by p90RSK. Altogether data show how p90RSK activates a self-reinforcing cell autonomous pro-adhesive circuit necessary for metastatic seeding of ovarian cancer cells. Thus, p90RSK inhibitors might hinder both the hematogenous and the peritoneal metastatic spread of human ovarian cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias Peritoneales / Proteínas Quinasas S6 Ribosómicas 90-kDa / Neoplasias Pulmonares Límite: Animals / Female / Humans Idioma: En Revista: Oncotarget Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias Peritoneales / Proteínas Quinasas S6 Ribosómicas 90-kDa / Neoplasias Pulmonares Límite: Animals / Female / Humans Idioma: En Revista: Oncotarget Año: 2016 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos