Pharmacological inhibition of mTORC2 reduces migration and metastasis in melanoma

Medientyp: E-Book; Sonderdruck

Titel: Pharmacological inhibition of mTORC2 reduces migration and metastasis in melanoma

Beteiligte: Günzle, Jessica [VerfasserIn]; Akasaka, Harue [VerfasserIn]; Jöchle, Katharina [VerfasserIn]; Reichardt, Wilfried [VerfasserIn]; Venkatasamy, Aïna [VerfasserIn]; Höppner, Jens [VerfasserIn]; Hellerbrand, Claus [VerfasserIn]; Fichtner-Feigl, Stefan [VerfasserIn]; Lang, Sven Arke [VerfasserIn]

Erschienen: Basel: MDPI AG, 2021

Umfang: 1 Online-Ressource (16 Seiten); Illustrationen, Diagramme; Supplementary material (1 PDF-Datei, 5 Seiten)

Sprache: Englisch

DOI: 10.3390/ijms22010030

ISSN: 1422-0067

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Beschreibung: 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

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