title: Identification of NOG as a specific breast cancer bone metastasis-supporting gene.
abstract: Metastasis requires numerous biological functions that jointly provide tumor cells from a primary site to seed and colonize a distant organ. Some of these activities are selected for in the primary site, whereas others are acquired at the metastatic niche. We provide molecular evidence showing that the BMP inhibitor, NOG, provides metastatic breast cancer cells with the ability to colonize the bone. NOG expression is acquired during the late events of metastasis, once cells have departed from the primary site, because it is not enriched in primary tumors with high risk of bone relapse. On the contrary, breast cancer bone metastatic lesions do select for high levels of NOG expression when compared with metastasis to the lung, liver, and brain. Pivotal to the bone colonization functions is the contribution of NOG to metastatic autonomous and nonautonomous cell functions. Using genetic approaches, we show that when NOG is expressed in human breast cancer cells, it facilitates bone colonization by fostering osteoclast differentiation and bone degradation and also contributes to metastatic lesions reinitiation. These findings reveal how aggressive cancer cell autonomous and nonautonomous functions can be mechanistically coupled to greater bone metastatic potential.
authors.affiliation: Oncology Programme, Institute for Research in Biomedicine, IRB-Barcelona, 08028 Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Tarragona
authors.forename: Milica
authors.initials: M
authors.lastname: Pavlovic
authors.forename: Anna
authors.initials: A
authors.lastname: Arnal-Estapé
authors.forename: Jelena
authors.initials: J
authors.lastname: Urosevic
authors.forename: Mònica
authors.initials: M
authors.lastname: Morales
authors.forename: Marc
authors.initials: M
authors.lastname: Guiu
authors.forename: Evarist
authors.initials: E
authors.lastname: Planet
authors.forename: Eva
authors.initials: E
authors.lastname: González-Suárez
authors.forename: Roger R
authors.initials: RR
authors.lastname: Gomis
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009928:Organ Specificity / Q000235:genetics; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D000099176:Noggin Protein
chemical_list: D002352:Carrier Proteins; D000099176:Noggin Protein