title: Focal adhesion signaling and therapy resistance in cancer.
abstract: Interlocking gene mutations, epigenetic alterations and microenvironmental features perpetuate tumor development, growth, infiltration and spread. Consequently, intrinsic and acquired therapy resistance arises and presents one of the major goals to solve in oncologic research today. Among the myriad of microenvironmental factors impacting on cancer cell resistance, cell adhesion to the extracellular matrix (ECM) has recently been identified as key determinant. Despite the differentiation between cell adhesion-mediated drug resistance (CAMDR) and cell adhesion-mediated radioresistance (CAMRR), the underlying mechanisms share great overlap in integrin and focal adhesion hub signaling and differ further downstream in the complexity of signaling networks between tumor entities. Intriguingly, cell adhesion to ECM is per se also essential for cancer cells similar to their normal counterparts. However, based on the overexpression of focal adhesion hub signaling receptors and proteins and a distinct addiction to particular integrin receptors, targeting of focal adhesion proteins has been shown to potently sensitize cancer cells to different treatment regimes including radiotherapy, chemotherapy and novel molecular therapeutics. In this review, we will give insight into the role of integrins in carcinogenesis, tumor progression and metastasis. Additionally, literature and data about the function of focal adhesion molecules including integrins, integrin-associated proteins and growth factor receptors in tumor cell resistance to radio- and chemotherapy will be elucidated and discussed.
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Dresden 01328, Germany; Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Eke
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Dresden 01328, Germany; Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute of Radiation Oncology, Helmholtz-Zentrum Dresden - Rossendorf, Dresden 01328, Germany. Electronic address: Nils.Cordes@OncoRay.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Cordes
mesh_terms: D002448:Cell Adhesion; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism*; D022001:Focal Adhesions; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction
chemical_list: D016023:Integrins
keywords: Extracellular matrix; Focal adhesion; Integrins; Small molecules; Targeted therapy