Your browser doesn't support javascript.
loading
The extracellular matrix and focal adhesion kinase signaling regulate cancer stem cell function in pancreatic ductal adenocarcinoma.
Begum, Asma; Ewachiw, Theodore; Jung, Clinton; Huang, Ally; Norberg, K Jessica; Marchionni, Luigi; McMillan, Ross; Penchev, Vesselin; Rajeshkumar, N V; Maitra, Anirban; Wood, Laura; Wang, Chenguang; Wolfgang, Christopher; DeJesus-Acosta, Ana; Laheru, Daniel; Shapiro, Irina M; Padval, Mahesh; Pachter, Jonathan A; Weaver, David T; Rasheed, Zeshaan A; Matsui, William.
Afiliación
  • Begum A; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Ewachiw T; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Jung C; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Huang A; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Norberg KJ; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Marchionni L; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • McMillan R; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Penchev V; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Rajeshkumar NV; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Maitra A; Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
  • Wood L; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Wang C; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Wolfgang C; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • DeJesus-Acosta A; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Laheru D; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Shapiro IM; Verastem, Inc., Needham, Massachusetts, United States of America.
  • Padval M; Verastem, Inc., Needham, Massachusetts, United States of America.
  • Pachter JA; Verastem, Inc., Needham, Massachusetts, United States of America.
  • Weaver DT; Verastem, Inc., Needham, Massachusetts, United States of America.
  • Rasheed ZA; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Matsui W; Departments of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One ; 12(7): e0180181, 2017.
Article en En | MEDLINE | ID: mdl-28692661
Cancer stem cells (CSCs) play an important role in the clonogenic growth and metastasis of pancreatic ductal adenocarcinoma (PDAC). A hallmark of PDAC is the desmoplastic reaction, but the impact of the tumor microenvironment (TME) on CSCs is unknown. In order to better understand the mechanisms, we examined the impact of extracellular matrix (ECM) proteins on PDAC CSCs. We quantified the effect of ECM proteins, ß1-integrin, and focal adhesion kinase (FAK) on clonogenic PDAC growth and migration in vitro and tumor initiation, growth, and metastasis in vivo in nude mice using shRNA and overexpression constructs as well as small molecule FAK inhibitors. Type I collagen increased PDAC tumor initiating potential, self-renewal, and the frequency of CSCs through the activation of FAK. FAK overexpression increased tumor initiation, whereas a dominant negative FAK mutant or FAK kinase inhibitors reduced clonogenic PDAC growth in vitro and in vivo. Moreover, the FAK inhibitor VS-4718 extended the anti-tumor response to gemcitabine and nab-paclitaxel in patient-derived PDAC xenografts, and the loss of FAK expression limited metastatic dissemination of orthotopic xenografts. Type I collagen enhances PDAC CSCs, and both kinase-dependent and independent activities of FAK impact PDAC tumor initiation, self-renewal, and metastasis. The anti-tumor impact of FAK inhibitors in combination with standard chemotherapy support the clinical testing of this combination.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Transducción de Señal / Carcinoma Ductal Pancreático / Proteína-Tirosina Quinasas de Adhesión Focal / Matriz Extracelular Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Células Madre Neoplásicas / Transducción de Señal / Carcinoma Ductal Pancreático / Proteína-Tirosina Quinasas de Adhesión Focal / Matriz Extracelular Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos