(Institución)/></a>
				</td>
				<td class= (Institución)
   (Nuevo usuario)
Ayuda  | Contacto  |  Castellano English  
 

Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Trombosis y hemostasia > DA - CIMA - Cardiovasculares - Trombosis y Hemostasia - Artículos de Revista >

Receptor of Activated Protein C Promotes Metastasis and Correlates with Clinical Outcome in Lung Adenocarcinoma
Autor(es) : Anton, I. (Iker)
Molina, E. (Eva)
Luis-Ravelo, D. (Diego)
Zandueta, C. (Carolina)
Valencia, K. (Karmele)
Ormazábal, C. (Cristina)
Martinez-Canarias, S. (Susana)
Perurena, N. (Naiara)
Pajares, M.J. (María José)
Agorreta, J. (Jackeline)
Montuenga, L.M. (Luis M.)
Segura, V. (Víctor)
Wistuba, I.I. (Ignacio I.)
Rivas, J. (Javier) de las
Hermida, J. (José)
Lecanda, F. (Fernando)
Palabras clave : Survival
Microenvironment
Bone Metastasis
Prognosis
Adrenal gland
Fecha incorporación: 2012
Editorial : American Thoracic Society
Versión del editor: http://ajrccm.atsjournals.org/content/early/2012/03/28/rccm.201110-1826OC
ISSN: 1535-4970
Cita: Anton I, Molina E, Luis-Ravelo D, Zandueta C, Valencia K, Ormazabal C, et al. Receptor of Activated Protein C Promotes Metastasis and Correlates with Clinical Outcome in Lung Adenocarcinoma. Am J Respir Crit Care Med 2012 Mar 29.
Resumen
RATIONALE: Efficient metastasis requires survival and adaptation of tumor cells to stringent conditions imposed by the extracellular milieu. Identification of critical survival signaling pathways in tumor cells might unveil novel targets relevant in disease progression. OBJECTIVES: To investigate the contribution of activated protein C (APC) and its receptor (EPCR) in animal models of lung cancer metastasis and in patients with lung adenocarcinoma. METHODS: Signaling pathway triggered by APC/EPCR and its relevance in apoptosis was studied in vitro. Functional significance was assessed by silencing and blocking antibodies in several in vivo models of lung cancer metastasis. We examined EPCR levels using a microarray dataset of 107 patients. Immunohistochemical analysis was performed in an independent cohort of 295 patients with lung adenocarcinoma. MEASUREMENTS AND MAIN RESULTS: The effects of APC binding to EPCR rapidly triggered Akt and ERK signaling pathways, leading to attenuated in vitro apoptosis. In vivo, silencing of EPCR expression or blocking APC/EPCR interaction reduced homing resulting in impaired prometastatic activity. Moreover, overexpression of EPCR induced an increase metastatic activity to target organs. Analysis of clinical samples showed a robust association between high EPCR levels and poor prognosis particularly in stage I patients. CONCLUSIONS: EPCR and its ligand APC promote cell survival that contributes to tumor cell endurance to stress favoring prometastatic activity of lung adenocarcinoma (ADC). EPCR/APC is a novel target of relevance in the clinical outcome of early-stage lung cancer.
Enlace permanente: http://hdl.handle.net/10171/21974
Aparece en las colecciones: DA - CIMA - Oncología - Adhesión y metástasis - Artículos de revista
DA - CIMA - Oncología - Biomarcadores - Artículos de Revista
DA - CIMA - Cardiovasculares - Trombosis y Hemostasia - Artículos de Revista

Ficheros en este registro:

No hay ficheros asociados a este ítem.

Los ítems de Dadun están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.