{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T17:48:13Z","timestamp":1768412893991,"version":"3.49.0"},"reference-count":57,"publisher":"Impact Journals, LLC","issue":"29","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncotarget"],"published-print":{"date-parts":[[2018,4,17]]},"DOI":"10.18632\/oncotarget.25003","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T10:26:56Z","timestamp":1523874416000},"page":"20563-20577","source":"Crossref","is-referenced-by-count":50,"title":["Inhibition of mTOR complex 2 restrains tumor angiogenesis in multiple myeloma"],"prefix":"10.18632","volume":"9","author":[{"given":"Aurelia","family":"Lamanuzzi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Saltarella","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Desantis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Antonia","family":"Frassanito","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, General Pathology Unit, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito","family":"Racanelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Nico","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Ribatti","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Section of Human Anatomy and Histology, University of Bari Aldo Moro Medical School, Bari, Italy"},{"name":"National Cancer Institute Giovanni Paolo II, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Ditonno","sequence":"additional","affiliation":[{"name":"Hematology Unit, Di Venere Hospital, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Prete","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Giovanni","family":"Solimando","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Dammacco","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Vacca","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Ria","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, Internal Medicine Unit G. Baccelli, University of Bari Aldo Moro Medical School, Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7892","published-online":{"date-parts":[[2018,4,17]]},"reference":[{"key":"1","first-page":"1227","article-title":"The role of the bone marrow microenvironment in multiple myeloma","volume":"20","author":"Vanderkerken","year":"2005","journal-title":"Histol Histopathol"},{"key":"2","first-page":"76","article-title":"Bone marrow angiogenesis and progression in multiple myeloma","volume":"1","author":"Vacca","year":"2011","journal-title":"Am J Blood Res"},{"key":"3","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1365-2141.1994.tb08304.x","article-title":"Bone marrow angiogenesis and progression in multiple myeloma","volume":"87","author":"Dammacco","year":"1994","journal-title":"Br J Haematol"},{"key":"4","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1182\/blood-2008-10-184226","article-title":"Induction of angiogenesis by normal and malignant plasma cells","volume":"114","author":"Bertsch","year":"2009","journal-title":"Blood"},{"key":"5","first-page":"184","article-title":"Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells","author":"Anderson","year":"2006","journal-title":"Cancer Res"},{"key":"6","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1053\/j.seminoncol.2005.06.018","article-title":"IMiDs: a novel class of immunomodulators","volume":"32","author":"Knight","year":"2005","journal-title":"Semin Oncol"},{"key":"7","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1158\/1078-0432.CCR-10-2381","article-title":"Lenalidomide restrains motility and overangiogenic potential of bone marrow endothelial cells in patients with active multiple myeloma","volume":"17","author":"Ditonno","year":"2011","journal-title":"Clin Cancer Res"},{"key":"8","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.ceb.2005.09.009","article-title":"Growing roles for the mTOR pathway","volume":"17","author":"Sabatini","year":"2005","journal-title":"Curr Opin Cell Biol"},{"key":"9","first-page":"e983402","article-title":"Regulation of global and specific mRNA translation by the mTOR signaling pathway","volume":"3","author":"Roux","year":"2015","journal-title":"Translation (Austin)"},{"key":"10","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.semcdb.2014.08.006","article-title":"mTOR and autophagy: a dynamic relationship governed by nutrients and energy","volume":"36","author":"Tee","year":"2014","journal-title":"Semin Cell Dev Biol"},{"key":"11","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/ncb1183","article-title":"Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive","volume":"6","author":"Hall","year":"2004","journal-title":"Nature Cell Biology"},{"key":"12","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1128\/MCB.00306-14","article-title":"Regulation of endothelial cell proliferation and vascular assembly through distinct mTORC2 signaling pathways","volume":"35","author":"Chen","year":"2015","journal-title":"Mol Cell Biol"},{"key":"13","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1106148","article-title":"Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex","volume":"307","author":"Sabatini","year":"2005","journal-title":"Science"},{"key":"14","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":"Huang","year":"2011","journal-title":"Curr Protein Pept Sci"},{"key":"15","first-page":"5027","article-title":"Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779","volume":"62","author":"Lichtenstein","year":"2002","journal-title":"Cancer Res"},{"key":"16","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1182\/blood-2003-05-1543","article-title":"Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone","volume":"103","author":"Jernberg-Wiklund","year":"2004","journal-title":"Blood"},{"key":"17","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1182\/blood-2004-06-2281","article-title":"Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma","volume":"104","author":"Anderson","year":"2004","journal-title":"Blood"},{"key":"18","first-page":"1483","article-title":"An open label phase I study of the safety and efficacy of RAD001 in combination with lenalidomide in the treatment of patients with relapsed and refractory multiple myeloma","volume":"114","author":"Laubach","year":"2009","journal-title":"Blood"},{"key":"19","first-page":"1266","article-title":"Phase I trial of CCI-779 (Temsirolimus) and weekly bortezomib in relapsed and\/or refractory multiple myeloma","volume":"112","author":"Vij","year":"2008","journal-title":"Blood"},{"key":"20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/mc.20628","article-title":"Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways","volume":"49","author":"Peng","year":"2010","journal-title":"Mol Carcinog"},{"key":"21","doi-asserted-by":"crossref","first-page":"6860","DOI":"10.1182\/blood-2011-03-342394","article-title":"Defining the role of TORC1\/2 in multiple myeloma","volume":"118","author":"Rodig","year":"2011","journal-title":"Blood"},{"key":"22","first-page":"8","article-title":"Current development of the second generation of mTOR inhibitors as anticancer agents","volume":"31","author":"Huang","year":"2012","journal-title":"Chin J Cancer"},{"key":"23","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nchembio.117","article-title":"Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases","volume":"4","author":"Knight","year":"2008","journal-title":"Nat Chem Biol"},{"key":"24","doi-asserted-by":"crossref","first-page":"e1000038","DOI":"10.1371\/journal.pbio.1000038","article-title":"Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2","volume":"7","author":"Shokat","year":"2009","journal-title":"PLoS Biol"},{"key":"25","doi-asserted-by":"crossref","first-page":"4560","DOI":"10.1182\/blood-2010-05-285726","article-title":"Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor","volume":"116","author":"Lichtenstein","year":"2010","journal-title":"Blood"},{"key":"26","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1158\/0008-5472.CAN-10-3126","article-title":"Reduced VEGF Production, Angiogenesis, and Vascular Regrowth Contribute to the Antitumor Properties of Dual mTORC1\/mTORC2 Inhibitors","volume":"71","author":"McDonald","year":"2011","journal-title":"Cancer Res"},{"key":"27","doi-asserted-by":"publisher","first-page":"36746","DOI":"10.18632\/oncotarget.5479","article-title":"Adiponectin promotes VEGF-A-dependent angiogenesis in human chondrosarcoma through PI3K, Akt, mTOR, and HIF-\u03b1 pathway","volume":"6","author":"Tang","year":"2015","journal-title":"Oncotarget"},{"key":"28","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1038\/onc.2014.164","article-title":"mTORC1 drives HIF-1\u03b1 and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3","volume":"34","author":"Tee","year":"2015","journal-title":"Oncogene"},{"key":"29","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.ccell.2015.10.004","article-title":"Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling","volume":"28","author":"Guan","year":"2015","journal-title":"Cancer Cell"},{"key":"30","first-page":"897025","article-title":"Mammalian Target of Rapamycin Inhibitors Induce Tumor Cell ApoptosisPrimarily by Inhibiting VEGF Expression and Angiogenesis","volume":"2013","author":"Lichtenstein","year":"2013","journal-title":"Journal of Oncology"},{"key":"31","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","article-title":"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor- independent pathway that regulates the cytoskeleton","volume":"14","author":"Sabatini","year":"2004","journal-title":"Curr Biol"},{"key":"32","doi-asserted-by":"publisher","first-page":"2954","DOI":"10.1038\/onc.2011.22","article-title":"Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis","volume":"30","author":"Bae","year":"2011","journal-title":"Oncogene"},{"key":"33","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1200\/JCO.2008.18.9514","article-title":"Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer","volume":"27","author":"Fuchs","year":"2009","journal-title":"Journal of Clinical Oncology"},{"key":"34","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1634\/theoncologist.2012-0378","article-title":"Multicenter Phase II Study of Tivozanib (AV-951) and Everolimus (RAD001) for Patients With Refractory, Metastatic Colorectal Cancer","volume":"18","author":"Blaszkowsky","year":"2013","journal-title":"The Oncologist"},{"key":"35","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1200\/JCO.2010.32.2321","article-title":"Phase I\/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy","volume":"29","author":"Sahin","year":"2011","journal-title":"Journal of Clinical Oncology"},{"key":"36","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1097\/JTO.0b013e3181ec1531","article-title":"Phase II Trial of Gefitinib and Everolimus in Advanced Non-small Cell Lung Cancer","volume":"5","author":"Miller","year":"2010","journal-title":"J Thorac Oncol"},{"key":"37","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1002\/iub.558","article-title":"mTORC1- and mTORC2-interacting proteins keep their multifunctional partners focused","volume":"63","author":"V\u00e1zquez-Prado","year":"2011","journal-title":"IUBMB Life"},{"key":"38","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ajh.24300","article-title":"TAK-228 (formerly MLN0128), an investigational oral dual TORC1\/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenstr\u00f6m\u2019s macroglobulinemia","volume":"91","author":"Wolf","year":"2016","journal-title":"Am J Hematol"},{"key":"39","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1111\/bjh.14529","article-title":"m-TOR inhibitors and their potential role in haematological malignancies","volume":"177","author":"Ferreri","year":"2017","journal-title":"Br J Haematol"},{"key":"40","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1478-811X-8-23","article-title":"Rac and Rho GTPases in cancer cell motility control","volume":"8","author":"Chiarugi","year":"2010","journal-title":"Cell Commun Signal"},{"key":"41","first-page":"782","article-title":"Endothelial Cell Migration During Angiogenesis","author":"Huot","year":"2007","journal-title":"Circ Res"},{"key":"42","first-page":"836","article-title":"Alpha(v)beta(3) integrin engagement enhances cell invasiveness in human multiple myeloma","volume":"87","author":"Dammacco","year":"2002","journal-title":"Haematologica"},{"key":"43","first-page":"a006478","article-title":"\u03b1v Integrins in Angiogenesis and Cancer","volume":"1","author":"Cheresh","year":"2011","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"44","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s12943-015-0396-z","article-title":"Significance of filamin A in mTORC2 function in glioblastoma","volume":"14","author":"Tamanoi","year":"2015","journal-title":"Molecular Cancer"},{"key":"45","first-page":"51","article-title":"PI3K\/AKT\/mTOR Pathway in Angiogenesis","volume":"4","author":"Maity","year":"2011","journal-title":"Front Mol Neurosci"},{"key":"46","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1872-034X.2008.00449.x","article-title":"Involvement of PI3K\/PTEN\/AKT\/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9","volume":"39","author":"Zhang","year":"2009","journal-title":"Hepatology Research"},{"key":"47","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1160\/TH04-06-0334","article-title":"A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in bone marrow endothelial cells of patients with multiple myeloma","volume":"92","author":"Dammacco","year":"2004","journal-title":"Thromb Haemost"},{"key":"48","doi-asserted-by":"crossref","first-page":"5796","DOI":"10.1158\/1078-0432.CCR-14-0847","article-title":"A HGF\/cMET autocrine loop is operative in multiple myeloma bone marrow endothelial cells and may represent a novel therapeutic target","volume":"20","author":"Rizzello","year":"2014","journal-title":"Clin Cancer Res"},{"key":"49","first-page":"233","article-title":"Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization","author":"Isner","year":"1998","journal-title":"Circ Res"},{"key":"50","doi-asserted-by":"crossref","first-page":"11205","DOI":"10.1073\/pnas.172161899","article-title":"Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival","volume":"99","author":"Lang","year":"2002","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yexcr.2014.10.017","article-title":"Angiopoietin-2 in Bone Marrow milieu promotes Multiple Myeloma-associated angiogenesis","volume":"330","author":"Ferrero","year":"2015","journal-title":"Exp Cell Res"},{"key":"52","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1158\/1078-0432.CCR-13-1950","article-title":"HIF-1\u03b1 of bone marrow endothelial cells implie relapse and drug resistance in patients with multiple myeloma and may act as a therapeutic target","volume":"20","author":"Guarini","year":"2014","journal-title":"Clin Cancer Res"},{"key":"53","doi-asserted-by":"crossref","first-page":"4371","DOI":"10.1158\/1078-0432.CCR-13-0039","article-title":"Novel targeting of phospho-cMet overcomes drug resistance and induces antitumor activity in multiple myeloma","volume":"19","author":"Ruggieri","year":"2013","journal-title":"Clin Cancer Res"},{"key":"54","doi-asserted-by":"crossref","first-page":"5334","DOI":"10.1200\/JCO.2005.03.723","article-title":"Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma","volume":"23","author":"Corradini","year":"2005","journal-title":"J Clin Oncol"},{"key":"55","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1046\/j.1365-2141.2003.04355.x","article-title":"Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group","volume":"121","author":"International Myeloma Working Group","year":"2003","journal-title":"Br J Haematol"},{"key":"56","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Schmittgen","year":"2001","journal-title":"Methods"},{"key":"57","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.2147\/OTT.S82453","article-title":"Combination of cetuximab and PP242 synergistically suppress the progression of wild-type KRAS colorectal carcinoma","volume":"8","author":"Qian","year":"2015","journal-title":"Onco Targets Ther"}],"container-title":["Oncotarget"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.25003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T01:28:57Z","timestamp":1720229337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.oncotarget.com\/lookup\/doi\/10.18632\/oncotarget.25003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,17]]},"references-count":57,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2018,4,17]]}},"alternative-id":["25003","29755672"],"URL":"https:\/\/doi.org\/10.18632\/oncotarget.25003","relation":{},"ISSN":["1949-2553"],"issn-type":[{"value":"1949-2553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,17]]}}}