title: Everolimus suppresses invasion and migration of renal cell carcinoma by inhibiting FAK activity and reversing epithelial to mesenchymal transition in vitro and in vivo.
abstract: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and the major cause of mortality in urological cancer. Most patients with RCC are asymptomatic until the disease is advanced and unresectable. In this situation, systemic therapy with immunotherapy or molecularly targeted therapy agents play an important role in therapeutic strategy. Everolimus (EVE), an m-TOR inhibitor, has the potential to inhibit tumor progression at multiple levels and is indicated for the treatment of advanced RCC in patients whose disease has metastasis. In this study, we provide molecular evidence associated with the antimetastatic effect of everolimus by demonstrating the suppression of lung metastasis of 786-O cells in mouse model. This effect was associated with reduced protein expressions of p-FAK (Tyr 925), p-Src (Tyr416), Vimentin, and RhoA and also with increased the E-cadherin protein expression. In summary, these findings provide new insights into the molecular mechanisms involved in the antimetastatic effect of everolimus and are thus valuable in the treatment of metastatic RCC.
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Division of Nephrology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Sheng-Wen
authors.initials: SW
authors.lastname: Wu
authors.affiliation: Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chin-Yin
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Division of Nephrology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Horng-Rong
authors.initials: HR
authors.lastname: Chang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D000068338:Everolimus / Q000494:pharmacology* / Q000627:therapeutic use; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D051379:Mice; D010766:Phosphorylation; D014746:Vimentin / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D014746:Vimentin; D000068338:Everolimus; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020742:rhoA GTP-Binding Protein
keywords: everolimus; invasion; metastasis; renal cell carcinoma