title: Molecular networks that regulate cancer metastasis.
abstract: Tumor metastases are responsible for approximately 90% of all cancer-related deaths. Although many patients can be cured, in the US and UK, cancer still causes 730,000 deaths every year, and it is second only to cardiovascular disease as a cause of death. The functional roles of many critical players involved in metastasis have been delineated in great detail in recent years, due to the draft of the human genome and to many associated discoveries. Here, we address several genetic events and critical factors that define the metastatic phenotype acquired during tumorigenesis. This involves molecular networks that promote local cancer-cell invasion, single-cell invasion, formation of the metastatic microenvironment of primary tumors, intravasation, lymphogenic metastasis, extravasation, and metastatic outgrowth. Altogether, these functional networks of molecules contribute to the development of a selective environment that promotes the seeding and malignant progression of tumorigenic cells in distant organs. We include here candidate target proteins and signaling pathways that are now under clinical investigation. Although many of these trials are still ongoing, they provide the basis for the development of new aspects in the treatment of metastatic cancers, which involves inhibition of these proteins and their molecular networks.
authors.affiliation: CEINGE, Biotecnologie Avanzate, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Spano
authors.forename: Chantal
authors.initials: C
authors.lastname: Heck
authors.forename: Pasqualino
authors.initials: P
authors.lastname: De Antonellis
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
authors.forename: Massimo
authors.initials: M
authors.lastname: Zollo
mesh_terms: D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D015870:Gene Expression; D053263:Gene Regulatory Networks; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics* / Q000502:physiology