{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:52:29Z","timestamp":1790268749723,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2127"],"award-info":[{"award-number":["FOR2127"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22010030","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T20:39:29Z","timestamp":1608669569000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Pharmacological Inhibition of mTORC2 Reduces Migration and Metastasis in Melanoma"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6008-3731","authenticated-orcid":false,"given":"Jessica","family":"Guenzle","sequence":"first","affiliation":[{"name":"Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harue","family":"Akasaka","sequence":"additional","affiliation":[{"name":"Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Joechle","sequence":"additional","affiliation":[{"name":"Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Reichardt","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK), 69120 Heidelberg, Germany"},{"name":"German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Department of Radiology Medical Physics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Killianstrasse 5a, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aina","family":"Venkatasamy","sequence":"additional","affiliation":[{"name":"Department of Radiology Medical Physics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Killianstrasse 5a, 79106 Freiburg, Germany"},{"name":"Service de Radiologie 1, H\u00f4pital de Hautepierre, H\u00f4pitaux Universitaires de Strasbourg, 1 Avenue Moli\u00e8re, 67098 Strasbourg, France"},{"name":"Laboratory Stress Response and Innovative Therapies \u201cStreinth\u201d, Inserm IRFAC UMR_S1113, Universit\u00e9 de Strasbourg, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-7446","authenticated-orcid":false,"given":"Jens","family":"Hoeppner","sequence":"additional","affiliation":[{"name":"Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Hellerbrand","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Friedrich\u2013Alexander University Erlangen-N\u00fcrnberg, Fahrstrasse 17, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Fichtner-Feigl","sequence":"additional","affiliation":[{"name":"Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany"},{"name":"Comprehensive Cancer Center Freiburg-CCCF, Medical Center-University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-5676","authenticated-orcid":false,"given":"Sven A.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany"},{"name":"Department of Surgery and Transplantation, University Hospital RWTH, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2174\/138920311795659407","article-title":"Role of mTOR signaling in tumor cell motility, invasion and metastasis","volume":"12","author":"Zhou","year":"2011","journal-title":"Curr. 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