title: Tension in Cancer.
abstract: Integrins represent a large family of cell receptors that mediate adhesion to the extracellular matrix (ECM), thereby modulating a variety of cellular functions that are required for proliferation, migration, malignant conversion and invasiveness. During tumorigenesis the conversion of a tumor cell from sessile, stationary phenotype to an invasive phenotype requires the ability of tumor cells to interact with their environment in order to transduce signals from the ECM into the cells. Hence, there is increasing evidence that changes in the composition, topography and tension of tumor matrix can be sensed by integrin receptors, leading to the regulation of intracellular signalling events which subsequently help to fuel cancer progression. The fact that intracellular signals perceived from integrin ligand binding impact on almost all steps of tumor progression, including tumor cell proliferation, survival, metastatic dissemination and colonization of a metastatic niche, renders integrins as ideal candidates for the development of therapeutic agents. In this review we summarize the role of integrins in cancer with the special focus on cancer therapies and the recent progress that has been made in the understanding of "integrin-induced tension in cancer". Finally, we conclude with clinical evidence for the role of integrin-mediated mechanotransduction in the development of therapy-resistant tumors.
authors.affiliation: Skin Cancer Unit of the Dermatology Department, Medical Faculty, West German Cancer Center, University Duisburg-Essen, 45147 Essen, Germany. stefanie.loeffek@uk-essen.de.|German Cancer Consortium (DKTK), University Duisburg-Essen, 45147 Essen, Germany. stefanie.loeffek@uk-essen.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Löffek
authors.affiliation: Department of Dermatology and Venerology, Medical Center, University of Freiburg, Hauptstraße 7, 79104 Freiburg, Germany. claus-werner.franzke@uniklinik-freiburg.de.
authors.forename: Claus-Werner
authors.initials: CW
authors.lastname: Franzke
authors.affiliation: Skin Cancer Unit of the Dermatology Department, Medical Faculty, West German Cancer Center, University Duisburg-Essen, 45147 Essen, Germany. iris.helfrich@uk-essen.de.|German Cancer Consortium (DKTK), University Duisburg-Essen, 45147 Essen, Germany. iris.helfrich@uk-essen.de.
authors.forename: Iris
authors.initials: I
authors.lastname: Helfrich
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D004548:Elasticity; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016023:Integrins; D016212:Transforming Growth Factor beta
keywords: TGF-β; drug-resistance; integrins; matrix stiffening; tumor progression