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LOXL2 promotes oncogenic progression in alveolar rhabdomyosarcoma independently of its catalytic activity.
Almacellas-Rabaiget, Olga; Monaco, Paola; Huertas-Martinez, Juan; García-Monclús, Silvia; Chicón-Bosch, Mariona; Maqueda-Marcos, Susana; Fabra-Heredia, Isabel; Herrero-Martín, David; Rello-Varona, Santiago; de Alava, Enrique; López-Alemany, Roser; Giangrande, Paloma H; Tirado, Oscar M.
Afiliação
  • Almacellas-Rabaiget O; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Monaco P; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Huertas-Martinez J; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • García-Monclús S; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Chicón-Bosch M; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Maqueda-Marcos S; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Fabra-Heredia I; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Herrero-Martín D; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; CIBERONC, Carlos III Institute of Health (ISCIII), Madrid, Spain.
  • Rello-Varona S; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • de Alava E; CIBERONC, Carlos III Institute of Health (ISCIII), Madrid, Spain; Laboratory of Molecular Pathology, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
  • López-Alemany R; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Giangrande PH; Department of Internal Medicine, Molecular and Cellular Biology Program, Abboud Cardiovascular Research Center, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA.
  • Tirado OM; Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; CIBERONC, Carlos III Institute of Health (ISCIII), Madrid, Spain; Institut Català D'Oncologia (ICO), L'Hospitalet de Llobregat, Barcelona, Spain. Electronic addre
Cancer Lett ; 474: 1-14, 2020 04 01.
Article em En | MEDLINE | ID: mdl-31911079
Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. Patients with the most aggressive histological variant have an unfavorable prognosis due to a high metastasis incidence. Lysyl oxidase-like 2 (LOXL2) is a lysyl oxidase, member of a family of extracellular matrix (ECM) crosslinking enzymes that recently have emerged as important regulators of tumor progression and metastasis. We report that LOXL2 is overexpressed in RMS, suggesting a potential role for LOXL2 in RMS oncogenic progression. Consistently, transient and stable LOXL2 knockdown decreased cell migratory and invasive capabilities in two ARMS cell lines. Furthermore, introduction of LOXL2 in RMS non-expressing cells using wild type or mutated (catalytically inactive) constructs resulted in increased cell migration, cell invasion and number and incidence of spontaneous lung metastasis in vivo, independently of its catalytic activity. To further study the molecular mechanism associated with LOXL2 expression, a pull-down assay on LOXL2-transfected cells was performed and analyzed by mass spectrometry. The intermediated filament protein vimentin was validated as a LOXL2-interactor. Thus, our results suggest an oncogenic role of LOXL2 in RMS by regulating cytoskeleton dynamics and cell motility capabilities.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Rabdomiossarcoma Alveolar / Carcinogênese / Aminoácido Oxirredutases / Neoplasias Pulmonares Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Rabdomiossarcoma Alveolar / Carcinogênese / Aminoácido Oxirredutases / Neoplasias Pulmonares Idioma: En Ano de publicação: 2020 Tipo de documento: Article