Pharmacological inhibition of mTORC2 reduces migration and metastasis in melanoma

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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

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: International journal of molecular sciences. - 22, 1 (2021) , 30, ISSN: 1422-0067

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2021

Creator: Günzle, Jessica
Akasaka, Harue
Jöchle, Katharina
Reichardt, Wilfried
Venkatasamy, Aïna
Höppner, Jens
Hellerbrand, Claus
Fichtner-Feigl, Stefan
Lang, Sven Arke

DOI: 10.3390/ijms22010030

URN: urn:nbn:de:bsz:25-freidok-1748021

Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:27 AM CEST

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2021

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