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Everolimus suppresses invasion and migration of renal cell carcinoma by inhibiting FAK activity and reversing epithelial to mesenchymal transition in vitro and in vivo
Author(s) -
Wu ShengWen,
Chen PeiNi,
Lin ChinYin,
Hsieh YihShou,
Chang HorngRong
Publication year - 2017
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22411
Subject(s) - reversing , mesenchymal stem cell , in vivo , epithelial–mesenchymal transition , everolimus , in vitro , cancer research , microbiology and biotechnology , chemistry , cell migration , cell , biology , transition (genetics) , medicine , biochemistry , materials science , gene , composite material
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.