title: Rac1 as a multifunctional therapeutic target to prevent and combat cancer metastasis.
abstract: Metastatic progression of malignant tumors resistant to conventional therapeutic approaches is an ultimate challenge in clinical oncology. Despite the efforts of basic and clinical researchers, there is still no effective treatment schedule to prevent or combat metastatic spread of malignant tumors. This report presents recent findings that could help in the development of targeted therapeutics directed against the most aggressive and treatment-resistant carcinoma cells. It was demonstrated that HNSCC carcinoma cell lines with acquired treatment resistance possessed increased number of cells with carcinoma stem cell (CSC) properties. Furthermore, resistant cells were characterized by increased expression of Rac1, enhanced cell migration, and accelerated release of proangio- and vasculogenic factors (VEGF-A) and influence on endothelial cell (HMEC-1) migration. Inhibition of Rac1 signaling in the treatment-resistant carcinoma cells can interrupt metastatic process due to anoikis restoration and decrease of cell migration. It is also suggested that carcinoma cells with repressed survival capacities will be characterized by reduced release of proangiogenic factors, resulting in the decrease of endothelial cell migration. Therefore targeting of Rac1-related pathways may be considered as a promising therapeutic approach to prevent or combat metastatic lesions.
authors.affiliation: Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Dept. of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Arnold
authors.affiliation: Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.|Assiut University, Dept. Pharmaceutical Organic Chemistry, Assiut, Egypt.
authors.forename: Alshaimaa
authors.initials: A
authors.lastname: Abdelmoez
authors.affiliation: Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Thurner
authors.affiliation: Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Debbage
authors.affiliation: Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Dept. of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Lukas
authors.affiliation: Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Dept. of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Sergej
authors.initials: S
authors.lastname: Skvortsov
authors.affiliation: Laboratory for Experimental and Translational Research on Radiation Oncology (EXTRO-Lab), Dept. of Therapeutic Radiology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Ira-Ida
authors.initials: II
authors.lastname: Skvortsova
keywords: Rac1; carcinoma stem cells; head and neck squamous cell carcinoma; metastasis; treatment resistance