{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:39:35Z","timestamp":1789875575712,"version":"4.0.1"},"reference-count":115,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T00:00:00Z","timestamp":1531180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Epithelioid hemangioendothelioma (EHE) is a rare soft-tissue sarcoma involving cells with histologic markers that suggest an endothelial origin. Around 90% of EHEs are caused by the fusion of Transcriptional Co-activator with a PDZ-motif (TAZ) with Calmodulin Binding Transcription Activator 1 (CAMTA1), a central nervous system-specific transcription activator. The 10% of EHEs that lack the TAZ\u2013CAMTA1 fusion instead have a fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3). YAP and TAZ are well-defined downstream effectors in the Hippo pathway that promote cell growth when translocated to the nucleus. The TAZ\u2013CAMTA1 fusion transcript is insensitive to the Hippo inhibitory signals that normally prevent this process and thus constitutively activates the TAZ transcriptome. In EHE, this causes tumors to form in a variety of organs and tissue types, most commonly the liver, lung, and bone. Its clinical course is unpredictable and highly variable. TAZ activation is known to contribute to key aspects of the cancer phenotype, including metastasis and fibrosis, and increased expression of TAZ is thought to be causally related to the progression of many cancers, including breast, lung, and liver. Therefore, understanding TAZ biology and the molecular mechanisms by which it promotes unregulated cell proliferation will yield insights and possibly improved treatments for both EHE as well as much more common cancers.<\/jats:p>","DOI":"10.3390\/cancers10070229","type":"journal-article","created":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T09:24:01Z","timestamp":1531214641000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Epithelioid Hemangioendothelioma as a Model of YAP\/TAZ-Driven Cancer: Insights from a Rare Fusion Sarcoma"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5406-8391","authenticated-orcid":false,"given":"John M.","family":"Lamar","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijeyaluxmy","family":"Motilal Nehru","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Illinois College of Medicine, and Jesse Brown VA Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,10]]},"reference":[{"key":"ref_1","unstructured":"Taleb, N.N. (2007). The Black Swan: The Impact of the Highly Improbable, Random House."},{"key":"ref_2","first-page":"221","article-title":"The incidence of alkaptonuria: A study in chemical individuality. 1902 [classical article]","volume":"75","author":"Garrod","year":"2002","journal-title":"Yale J. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/gcc.22073","article-title":"Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma","volume":"52","author":"Antonescu","year":"2013","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/onc.2015.148","article-title":"Mechanism of action of a WWTR1(TAZ)-CAMTA1 fusion oncoprotein","volume":"35","author":"Tanas","year":"2016","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Warren, J.S.A., Xiao, Y., and Lamar, J.M. (2018). YAP\/TAZ activation as a target for treating metastatic cancer. Cancers, 10.","DOI":"10.3390\/cancers10040115"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/j.cellsig.2016.08.004","article-title":"The roles of the hippo pathway in cancer metastasis","volume":"28","author":"Yang","year":"2016","journal-title":"Cell Signal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the roots of cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.cell.2015.10.044","article-title":"Hippo pathway in organ size control, tissue homeostasis, and cancer","volume":"163","author":"Yu","year":"2015","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1378\/chest.11-0039","article-title":"Clinical patterns and outcome in epithelioid hemangioendothelioma with or without pulmonary involvement: Insights from an internet registry in the study of a rare cancer","volume":"140","author":"Lau","year":"2011","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1084\/jem.10.5.575","article-title":"The results of the application of special histological methods to the study of tumors","volume":"10","author":"Mallory","year":"1908","journal-title":"J. Exp. Med."},{"key":"ref_11","first-page":"259","article-title":"Epithelioid hemangioendothelioma: An overview and update on a rare vascular tumor","volume":"8","author":"Sardaro","year":"2014","journal-title":"Oncol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1002\/1097-0142(19820901)50:5<970::AID-CNCR2820500527>3.0.CO;2-Z","article-title":"Epithelioid hemangioendothelioma: A vascular tumor often mistaken for a carcinoma","volume":"50","author":"Weiss","year":"1982","journal-title":"Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/path.1711280308","article-title":"Histogenesis of the so-called \u201cintravascular bronchioloalveolar tumour\u201d","volume":"128","author":"Corrin","year":"1979","journal-title":"J. Pathol."},{"key":"ref_14","first-page":"174","article-title":"Angiogenic nature of the \u201cintravascular bronchioloalveolar tumor\u201d of the lung: An electron microscopic study","volume":"105","author":"Victor","year":"1981","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/(SICI)1097-0142(19990201)85:3<562::AID-CNCR7>3.0.CO;2-T","article-title":"Epithelioid hemangioendothelioma of the liver: A clinicopathologic study of 137 cases","volume":"85","author":"Makhlouf","year":"1999","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1097\/PAS.0b013e31815bf8e6","article-title":"Epithelioid hemangioendothelioma of soft tissue: A proposal for risk stratification based on 49 cases","volume":"32","author":"Deyrup","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/jso.23517","article-title":"Does histology predict outcome for malignant vascular tumors of the liver?","volume":"109","author":"Groeschl","year":"2014","journal-title":"J. Surg. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1038\/modpathol.2013.176","article-title":"Malignant vascular tumors\u2014An update","volume":"27","author":"Antonescu","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/1746-1596-9-131","article-title":"Epithelioid hemangioendothelioma: Clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases","volume":"9","author":"Flucke","year":"2014","journal-title":"Diagn. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/PAS.0000000000000511","article-title":"Nuclear expression of camta1 distinguishes epithelioid hemangioendothelioma from histologic mimics","volume":"40","author":"Doyle","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/his.12713","article-title":"CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma","volume":"67","author":"Shibuya","year":"2015","journal-title":"Histopathology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1097\/00000478-200105000-00019","article-title":"Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma","volume":"25","author":"Mendlick","year":"2001","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/gcc.20886","article-title":"A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites","volume":"50","author":"Errani","year":"2011","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"98ra82","DOI":"10.1126\/scitranslmed.3002409","article-title":"Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma","volume":"3","author":"Tanas","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1111\/his.12697","article-title":"Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants","volume":"67","author":"Patel","year":"2015","journal-title":"Histopathology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/PAS.0000000000000346","article-title":"Thoracic epithelioid malignant vascular tumors: A clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of WWTR1-CAMTA1 fusions","volume":"39","author":"Anderson","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1242\/dev.102376","article-title":"The hippo pathway effectors TAZ and YAP in development, homeostasis and disease","volume":"141","author":"Varelas","year":"2014","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ceb.2017.12.012","article-title":"The hippo pathway in organ development, homeostasis, and regeneration","volume":"49","author":"Fu","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1152\/physrev.00005.2014","article-title":"The biology of YAP\/TAZ: Hippo signaling and beyond","volume":"94","author":"Piccolo","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1158\/1078-0432.1119.11.3","article-title":"Allelic losses at 1p36 and 19q13 in gliomas: Correlation with histologic classification, definition of a 150-kb minimal deleted region on 1p36, and evaluation of CAMTA1 as a candidate tumor suppressor gene","volume":"11","author":"Barbashina","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.ejca.2006.09.023","article-title":"Allelic variants of CAMTA1 and FLJ10737 within a commonly deleted region at 1p36 in neuroblastoma","volume":"43","author":"Henrich","year":"2007","journal-title":"Eur. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1158\/1078-0432.CCR-05-1431","article-title":"Reduced expression of camta1 correlates with adverse outcome in neuroblastoma patients","volume":"12","author":"Henrich","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1038\/emboj.2011.301","article-title":"CAMTA1 is a novel tumour suppressor regulated by miR-9\/9* in glioblastoma stem cells","volume":"30","author":"Schraivogel","year":"2011","journal-title":"EMBO J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1101\/lm.041111.115","article-title":"The calmodulin-binding transcription activator camta1 is required for long-term memory formation in mice","volume":"23","author":"Tan","year":"2016","journal-title":"Learn. Mem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1136\/jmedgenet-2012-100856","article-title":"Intragenic camta1 rearrangements cause non-progressive congenital ataxia with or without intellectual disability","volume":"49","author":"Thevenon","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1093\/hmg\/ddm097","article-title":"Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance","volume":"16","author":"Huentelman","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/cge.12407","article-title":"Intragenic camta1 deletions are associated with a spectrum of neurobehavioral phenotypes","volume":"87","author":"Shinawi","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11521","DOI":"10.1073\/pnas.1411251111","article-title":"Ataxia and purkinje cell degeneration in mice lacking the CAMTA1 transcription factor","volume":"111","author":"Long","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21253","DOI":"10.1074\/jbc.M701223200","article-title":"A potential dimerization region of dcamta is critical for termination of fly visual response","volume":"282","author":"Gong","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Muller-Borer, B., Esch, G., Aldina, R., Woon, W., Fox, R., Bursac, N., Hiller, S., Maeda, N., Shepherd, N., and Jin, J.P. (2012). Calcium dependent camta1 in adult stem cell commitment to a myocardial lineage. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038454"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1158\/0008-5472.CAN-10-3014","article-title":"CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programs in neuroblastoma cells","volume":"71","author":"Henrich","year":"2011","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13355","DOI":"10.1074\/jbc.M900843200","article-title":"Tead transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition","volume":"284","author":"Zhang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6778","DOI":"10.1093\/emboj\/19.24.6778","article-title":"Taz: A novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins","volume":"19","author":"Kanai","year":"2000","journal-title":"EMBO J."},{"key":"ref_44","first-page":"121","article-title":"The hippo signal transduction pathway in soft tissue sarcomas","volume":"1856","author":"Mohamed","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.phrs.2015.11.025","article-title":"Targeting the hippo pathway: Clinical implications and therapeutics","volume":"103","author":"Ye","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.bbrc.2017.05.032","article-title":"TEAD1 mediates the oncogenic activities of Hippo-YAP1 signaling in osteosarcoma","volume":"488","author":"Chai","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2539","DOI":"10.1038\/cddis.2016.468","article-title":"The TAZ-miR-224-SMAD4 axis promotes tumorigenesis in osteosarcoma","volume":"8","author":"Ma","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1158\/1541-7786.MCR-17-0004","article-title":"A novel notch-YAP circuit drives stemness and tumorigenesis in embryonal rhabdomyosarcoma","volume":"15","author":"Slemmons","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1172\/JCI67087","article-title":"Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via hippo pathway suppression","volume":"124","author":"Crose","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Slemmons, K.K., Crose, L.E., Rudzinski, E., Bentley, R.C., and Linardic, C.M. (2015). Role of the YAP Oncoprotein in Priming Ras-Driven Rhabdomyosarcoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140781"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ccr.2014.05.029","article-title":"The hippo transducer yap1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation","volume":"26","author":"Tremblay","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/path.4745","article-title":"The hippo effector TAZ (WWTR1) transforms myoblasts and its abundance is associated with reduced survival in embryonal rhabdomyosarcoma","volume":"240","author":"Mohamed","year":"2016","journal-title":"J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2616","DOI":"10.1158\/1078-0432.CCR-17-1207","article-title":"The transcriptional coactivator taz is a potent mediator of alveolar rhabdomyosarcoma tumorigenesis","volume":"24","author":"Deel","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_54","first-page":"E3402","article-title":"Deregulation of the hippo pathway in soft-tissue sarcoma promotes foxm1 expression and tumorigenesis","volume":"112","author":"Mucaj","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3389\/fonc.2015.00190","article-title":"A review: Molecular aberrations within hippo signaling in bone and soft-tissue sarcomas","volume":"5","author":"Deel","year":"2015","journal-title":"Front. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"30094","DOI":"10.18632\/oncotarget.8979","article-title":"TAZ and YAP are frequently activated oncoproteins in sarcomas","volume":"7","author":"Fullenkamp","year":"2016","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18277","DOI":"10.1038\/srep18277","article-title":"A YAP\/TAZ-miR-130\/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions","volume":"5","author":"Bertero","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1096\/fj.201700722R","article-title":"Deregulation of Hippo-TAZ pathway during renal injury confers a fibrotic maladaptive phenotype","volume":"32","author":"Anorga","year":"2018","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1681\/ASN.2015121354","article-title":"YAP\/TAZ deletion in Gli(+) cell-derived myofibroblasts attenuates fibrosis","volume":"28","author":"Liang","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"L344","DOI":"10.1152\/ajplung.00300.2014","article-title":"Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis","volume":"308","author":"Liu","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"42595","DOI":"10.1038\/srep42595","article-title":"Taz contributes to pulmonary fibrosis by activating profibrotic functions of lung fibroblasts","volume":"7","author":"Noguchi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jid.2017.08.024","article-title":"Therapeutic targeting of TAZ and YAP by dimethyl fumarate in systemic sclerosis fibrosis","volume":"138","author":"Toyama","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1681\/ASN.2015050499","article-title":"YAP\/TAZ are mechanoregulators of TGF-Beta-Smad signaling and renal fibrogenesis","volume":"27","author":"Szeto","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14902","DOI":"10.1074\/jbc.M117.780502","article-title":"TGF-Beta1 regulates the expression and transcriptional activity of TAZ protein via a SMAD3-independent, myocardin-related transcription factor-mediated mechanism","volume":"292","author":"Miranda","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"C277","DOI":"10.1152\/ajpcell.00205.2016","article-title":"Taz activation drives fibroblast spheroid growth, expression of profibrotic paracrine signals, and context-dependent ecm gene expression","volume":"312","author":"Jorgenson","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/ncb2756","article-title":"Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts","volume":"15","author":"Calvo","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1101\/gad.304501.117","article-title":"Mutual dependence of the MRTF-SRF and YAP-TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics","volume":"31","author":"Foster","year":"2017","journal-title":"Genes Dev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"389","DOI":"10.7150\/ijbs.13688","article-title":"Proton-sensing gpcr-yap signalling promotes cancer-associated fibroblast activation of mesenchymal stem cells","volume":"12","author":"Zhu","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s11373-008-9264-9","article-title":"Connective tissue growth factor (CTGF) and cancer progression","volume":"15","author":"Chu","year":"2008","journal-title":"J. Biomed. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12079-009-0071-5","article-title":"Connective tissue growth factor (CCN2, CTGF) and organ fibrosis: Lessons from transgenic animals","volume":"4","author":"Brigstock","year":"2010","journal-title":"J. Cell Commun. Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1139\/o03-069","article-title":"The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biology","volume":"81","author":"Leask","year":"2003","journal-title":"Biochem. Cell Biol."},{"key":"ref_72","first-page":"69","article-title":"Liver transplant for nonhepatocellular carcinoma malignancy","volume":"15","year":"2017","journal-title":"Exp. Clin. Transplant."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s12029-014-9590-2","article-title":"Liver transplantation for malignancies","volume":"45","author":"Eghtesad","year":"2014","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1177\/152692480701700112","article-title":"Liver transplantation for hepatic epithelioid hemangioendothelioma: A case series","volume":"17","author":"Bufton","year":"2007","journal-title":"Prog. Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1002\/cncr.22225","article-title":"Primary malignant hepatic epithelioid hemangioendothelioma: A comprehensive review of the literature with emphasis on the surgical therapy","volume":"107","author":"Mehrabi","year":"2006","journal-title":"Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1097\/TP.0000000000001603","article-title":"Hepatic epithelioid hemangioendothelioma and adult liver transplantation: Proposal for a prognostic score based on the analysis of the ELTR-ELITA registry","volume":"101","author":"Lai","year":"2017","journal-title":"Transplantation"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11864-018-0536-y","article-title":"Epithelioid hemangioendothelioma: Update on diagnosis and treatment","volume":"19","author":"Rosenberg","year":"2018","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1159\/000227683","article-title":"Successful medical treatment of an epithelioid hemangioendothelioma of liver","volume":"54","author":"Idilman","year":"1997","journal-title":"Oncology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.3892\/ol.2013.1217","article-title":"Treatment of pulmonary epithelioid hemangioendothelioma with combination chemotherapy: Report of three cases and review of the literature","volume":"5","author":"Ye","year":"2013","journal-title":"Oncol. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1177\/1758834015582206","article-title":"Combination capecitabine and bevacizumab in the treatment of metastatic hepatic epithelioid hemangioendothelioma","volume":"7","author":"Lau","year":"2015","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1034\/j.1399-3003.1999.14a40.x","article-title":"Aggressive form of pleural epithelioid haemangioendothelioma: Complete response after chemotherapy","volume":"14","author":"Pinet","year":"1999","journal-title":"Eur. Respir. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1111\/j.1752-699X.2010.00221.x","article-title":"Primary pleural epithelioid hemangioendothelioma (EHE)\u2014Two cases and review of the literature","volume":"5","author":"Lazarus","year":"2011","journal-title":"Clin. Respir. J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Semenisty, V., Naroditsky, I., Keidar, Z., and Bar-Sela, G. (2015). Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma\u2014A suitable treatment option: Case report and review of anti-angiogenic treatment options. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1395-6"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1159\/000443986","article-title":"Sorafenib monotherapy in a patient with unresectable hepatic epithelioid hemangioendothelioma","volume":"9","author":"Kobayashi","year":"2016","journal-title":"Case Rep. Oncol."},{"key":"ref_85","first-page":"133","article-title":"Activity of angiogenesis inhibitors in metastatic epithelioid hemangioendothelioma: A case report","volume":"9","author":"Gaur","year":"2012","journal-title":"Cancer Biol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/annonc\/mds237","article-title":"An open-label, multicenter, phase ii study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas","volume":"24","author":"Agulnik","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e8507","DOI":"10.1097\/MD.0000000000008507","article-title":"Apatinib for the treatment of pulmonary epithelioid hemangioendothelioma: A case report and literature review","volume":"96","author":"Zheng","year":"2017","journal-title":"Medicine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1186\/1752-1947-4-413","article-title":"Successful treatment of metastatic hepatic epithelioid hemangioendothelioma with thalidomide: A case report","volume":"4","author":"Raphael","year":"2010","journal-title":"J. Med. Case Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1665-2681(19)31596-0","article-title":"Thalidomide for the treatment of metastatic hepatic epithelioid hemangioendothelioma: A case report with a long term follow-up","volume":"10","author":"Salech","year":"2011","journal-title":"Ann. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e00191","DOI":"10.1002\/rcr2.191","article-title":"Pemetrexed for epithelioid haemangioendothelioma of the pleura","volume":"4","author":"Kanemura","year":"2016","journal-title":"Respirol. Case Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1245\/s10434-016-5331-z","article-title":"Sirolimus in advanced epithelioid hemangioendothelioma: A retrospective case-series analysis from the italian rare cancer network database","volume":"23","author":"Stacchiotti","year":"2016","journal-title":"Ann. Surg. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/cr.2015.140","article-title":"The hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to MTORC1","volume":"25","author":"Hansen","year":"2015","journal-title":"Cell Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1101\/gad.192856.112","article-title":"Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP","volume":"26","author":"Huang","year":"2012","journal-title":"Genes Dev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.2174\/0929867323666160316125048","article-title":"Non-photoinduced biological properties of verteporfin","volume":"23","author":"Gibault","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.ccr.2014.04.017","article-title":"Mutant Gq\/11 promote uveal melanoma tumorigenesis by activating YAP","volume":"25","author":"Yu","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1111\/jcmm.13182","article-title":"Targeting YAP in malignant pleural mesothelioma","volume":"21","author":"Zhang","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5371","DOI":"10.2147\/OTT.S109979","article-title":"Verteporfin, a suppressor of yap-tead complex, presents promising antitumor properties on ovarian cancer","volume":"9","author":"Feng","year":"2016","journal-title":"OncoTargets Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ncb2936","article-title":"Metabolic control of YAP and TAZ by the mevalonate pathway","volume":"16","author":"Sorrentino","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_99","first-page":"E89","article-title":"Interplay of mevalonate and hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility","volume":"111","author":"Wang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1177\/2050640615583587","article-title":"A phase ii study of TRC105 in patients with hepatocellular carcinoma who have progressed on sorafenib","volume":"3","author":"Duffy","year":"2015","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.clgc.2016.05.010","article-title":"A phase ii clinical trial of TRC105 (anti-endoglin antibody) in adults with advanced\/metastatic urothelial carcinoma","volume":"15","author":"Apolo","year":"2017","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_102","unstructured":"Brian, R. Personal Communication."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1158\/0008-5472.CAN-17-3139","article-title":"The hippo pathway component TAZ promotes immune evasion in human cancer through PD-L1","volume":"78","author":"Azad","year":"2018","journal-title":"Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Kim, M.H., Kim, C.G., Kim, S.K., Shin, S.J., Choe, E.A., Park, S.H., Shin, E.C., and Kim, J. (2018). YAP-induced PD-L1 expression drives immune evasion in brafi-resistant melanoma. Cancer Immunol. Res.","DOI":"10.1158\/2326-6066.CIR-17-0320"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.bbrc.2017.07.007","article-title":"Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma","volume":"491","author":"Lee","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"114576","DOI":"10.18632\/oncotarget.23051","article-title":"YAP regulates PD-L1 expression in human NSCLC cells","volume":"8","author":"Miao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00018-014-1742-9","article-title":"The mammalian hippo pathway: Regulation and function of YAP1 and TAZ","volume":"72","author":"Kodaka","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"26245","DOI":"10.1074\/jbc.M112.382036","article-title":"The n-terminal phosphodegron targets TAZ\/WWTR1 protein for SCFBeta-TrCP-dependent degradation in response to phosphatidylinositol 3-kinase inhibition","volume":"287","author":"Huang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1101\/gad.2000111","article-title":"Angiomotin is a novel hippo pathway component that inhibits YAP oncoprotein","volume":"25","author":"Zhao","year":"2011","journal-title":"Genes Dev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.celrep.2015.09.014","article-title":"Tankyrase inhibitors target YAP by stabilizing angiomotin family proteins","volume":"13","author":"Wang","year":"2015","journal-title":"Cell Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"28765","DOI":"10.18632\/oncotarget.9117","article-title":"Angiomotin stabilization by tankyrase inhibitors antagonizes constitutive tead-dependent transcription and proliferation of human tumor cells with hippo pathway core component mutations","volume":"7","author":"Troilo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"15256","DOI":"10.1074\/jbc.M116.722967","article-title":"Tankyrase inhibitor sensitizes lung cancer cells to endothelial growth factor receptor (EGFR) inhibition via stabilizing angiomotins and inhibiting YAP signaling","volume":"291","author":"Wang","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Jia, J., Qiao, Y., Pilo, M.G., Cigliano, A., Liu, X., Shao, Z., Calvisi, D.F., and Chen, X. (2017). Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the hippo cascade. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184068"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1158\/1078-0432.CCR-04-1773","article-title":"Down-regulation of LATS1 and LATS2 mrna expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers","volume":"11","author":"Takahashi","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/mc.20317","article-title":"Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma","volume":"46","author":"Seidel","year":"2007","journal-title":"Mol. Carcinog."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/7\/229\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:11:18Z","timestamp":1760195478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/10\/7\/229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,10]]},"references-count":115,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["cancers10070229"],"URL":"https:\/\/doi.org\/10.3390\/cancers10070229","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,10]]}}}