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Google圖書搜尋
Pharmacological Inhibition of MTORC2 Reduces Migration and Metastasis in Melanoma
Jessica Günzle
Harue Akasaka
Katharina Jöchle
Wilfried Reichardt
Aïna Venkatasamy
Jens Höppner
Claus Hellerbrand
Stefan Fichtner-Feigl
Sven Arke Lang
出版
Universität
, 2021
URL
http://books.google.com.hk/books?id=u7hEzgEACAAJ&hl=&source=gbs_api
註釋
Abstract: Despite recent advances in therapy, liver metastasis from melanoma is still associated with poor prognosis. Although targeting the mTOR signaling pathway exerts potent anti-tumor activity, little is known about specific mTORC2 inhibition regarding liver metastasis. Using the novel mTORC2 specific inhibitor JR-AB2-011, we show significantly reduced migration and invasion capacity by impaired activation of MMP2 in melanoma cells. In addition, blockade of mTORC2 induces cell death by non-apoptotic pathways and reduces tumor cell proliferation rate dose-dependently. Furthermore, a significant reduction of liver metastasis was detected in a syngeneic murine metastasis model upon therapy with JR-AB2-011 as determined by in vivo imaging and necropsy. Hence, our study for the first time highlights the impact of the pharmacological blockade of mTORC2 as a potent novel anti-cancer approach for liver metastasis from melanoma