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Annual Review of Cancer Biology

Volume 8, 2024

YAP, TAZ, and Hippo-Dysregulating Fusion Proteins in Cancer

Abstract

Gene fusions are well-known drivers of cancer and are potent targets for molecular therapy. An emerging spectrum of human tumors harbors recurrent and pathognomonic gene fusions that involve the transcriptional coactivator (which encodes the protein YAP) or its paralog (which encodes the protein TAZ). YAP and TAZ are frequently activated in cancer and are the transcriptional effectors of the Hippo pathway, a highly conserved kinase cascade that regulates diverse functions such as organ size, development, and homeostasis. In this review, we discuss the tumors that have YAP, TAZ, or other Hippo-dysregulating fusion proteins; the mechanisms of these fusion proteins in driving their respective tumors; and the potential vulnerabilities of these chimeric oncoproteins across cancers of many origins. Furthermore, as new and gene fusions are discovered, we provide a framework to predict whether the resulting protein product is likely to be oncogenic.

Keyword(s): cancer, gene fusions, Hippo pathway, sarcoma, WWTR1/TAZ, YAP1
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/content/journals/10.1146/annurev-cancerbio-061223-094639
2024-06-12
2024-07-03
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Literature Cited

  1. Agaimy A, Stoehr R, Michal M, Christopoulos P, Winter H, et al. 2021.. Recurrent YAP1-TFE3 gene fusions in clear cell stromal tumor of the lung. . Am. J. Surg. Pathol. 45::1541–49
     [Crossref] [Google Scholar]
  2. Agnihotri S, Suppiah S, Tonge PD, Jalali S, Danesh A, et al. 2017.. Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas. . Nat. Commun. 8::186
     [Crossref] [Google Scholar]
  3. Alberti S, Hyman AA. 2021.. Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing. . Nat. Rev. Mol. Cell Biol. 22::196–213
     [Crossref] [Google Scholar]
  4. Anderson WJ, Fletcher CDM, Hornick JL. 2021.. Loss of expression of YAP1 C-terminus as an ancillary marker for epithelioid hemangioendothelioma variant with YAP1-TFE3 fusion and other YAP1-related vascular neoplasms. . Modern Pathol. 34::2036–42
     [Crossref] [Google Scholar]
  5. Antonescu CR, Chen H-W, Zhang L, Sung Y-S, Panicek D, et al. 2014.. ZFP36-FOSB fusion defines a subset of epithelioid hemangioma with atypical features. . Genes Chromosom. Cancer 53::951–59
     [Crossref] [Google Scholar]
  6. Antonescu CR, Dickson BC, Sung Y-S, Zhang L, Suurmeijer AJH, et al. 2020.. Recurrent YAP1 and MAML2 gene rearrangements in retiform and composite hemangioendothelioma. . Am. J. Surg. Pathol. 44::1677–84
     [Crossref] [Google Scholar]
  7. Antonescu CR, Le Loarer F, Mosquera J-M, Sboner A, Zhang L, et al. 2013.. Novel YAP1-TFE3 fusion defines a distinct subset of epithelioid hemangioendothelioma. . Genes Chromosom. Cancer 52::775–84
     [Crossref] [Google Scholar]
  8. Arabzade A, Zhao Y, Varadharajan S, Chen HC, Jessa S, et al. 2021.. ZFTA-RELA dictates oncogenic transcriptional programs to drive aggressive supratentorial ependymoma. . Cancer Discov. 11::2200–15
     [Crossref] [Google Scholar]
  9. Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, et al. 2002.. PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1)(p11.2;q21). . Am. J. Surg. Pathol. 26::1553–66
     [Crossref] [Google Scholar]
  10. Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, et al. 2001.. Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. . Am. J. Pathol. 159::179–92
     [Crossref] [Google Scholar]
  11. Argani P, Lui MY, Couturier J, Bouvier R, Fournet JC, Ladanyi M. 2003.. A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). . Oncogene 22::5374–78
     [Crossref] [Google Scholar]
  12. Banani SF, Lee HO, Hyman AA, Rosen MK. 2017.. Biomolecular condensates: organizers of cellular biochemistry. . Nat. Rev. Mol. Cell Biol. 18::285–98
     [Crossref] [Google Scholar]
  13. Bataller A, Guijarro F, Caye-Eude A, Strullu M, Sterin A, et al. 2021.. KMT2A-CBL rearrangements in acute leukemias: clinical characteristics and genetic breakpoints. . Blood Adv. 5::5617–20
     [Crossref] [Google Scholar]
  14. Berthold R, Isfort I, Erkut C, Heinst L, Grunewald I, et al. 2022.. Fusion protein-driven IGF-IR/PI3K/AKT signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma. . Oncogenesis 11::20
     [Crossref] [Google Scholar]
  15. Boulay G, Sandoval GJ, Riggi N, Iyer S, Buisson R, et al. 2017.. Cancer-specific retargeting of BAF complexes by a prion-like domain. . Cell 171::163–78.e19
     [Crossref] [Google Scholar]
  16. Cai J, Song X, Wang W, Watnick T, Pei Y, et al. 2018.. A RhoA–YAP–c-Myc signaling axis promotes the development of polycystic kidney disease. . Genes Dev. 32::781–93
     [Crossref] [Google Scholar]
  17. Castellan M, Guarnieri A, Fujimura A, Zanconato F, Battilana G, et al. 2021.. Single-cell analyses reveal YAP/TAZ as regulators of stemness and cell plasticity in glioblastoma. . Nat. Cancer 2::174–88
     [Crossref] [Google Scholar]
  18. Chang L, Azzolin L, Di Biagio D, Zanconato F, Battilana G, et al. 2018.. The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ. . Nature 563::265–69
     [Crossref] [Google Scholar]
  19. Chen Q, Zhang N, Xie R, Wang W, Cai J, et al. 2015.. Homeostatic control of Hippo signaling activity revealed by an endogenous activating mutation in YAP. . Genes Dev. 29::1285–97
     [Crossref] [Google Scholar]
  20. Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, et al. 2011.. The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. . Cell 147::759–72
     [Crossref] [Google Scholar]
  21. Crose LES, Galindo KA, Kephart JG, Chen C, Fitamant J, et al. 2014.. Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression. . J. Clin. Investig. 124::285–96
     [Crossref] [Google Scholar]
  22. Dashti NK, Dermawan JK, Schoolmeester JK, Halling KC, Antonescu CR. 2022.. A novel WWTR1::AFF2 fusion in an intra-abdominal soft tissue sarcoma with associated endometriosis. . Genes Chromosom. Cancer 61::497–502
     [Crossref] [Google Scholar]
  23. Dehner CA, Sadegh D, Boulos F, Messias N, Wang WL, et al. 2022.. Clear cell stromal tumour of the lung with YAP1::TFE3 fusion: four cases including a case with highly aggressive clinical course. . Histopathology 81::239–45
     [Crossref] [Google Scholar]
  24. Dermawan JK, Azzato EM, Billings SD, Fritchie KJ, Aubert S, et al. 2021a.. YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases. . Modern Pathol. 34::2211–21
     [Crossref] [Google Scholar]
  25. Dermawan JK, Azzato EM, McKenney JK, Liegl-Atzwanger B, Rubin BP. 2021b.. YAP1–TFE3 gene fusion variant in clear cell stromal tumour of lung: report of two cases in support of a distinct entity. . Histopathology 79::940–46
     [Crossref] [Google Scholar]
  26. Dermawan JK, DiNapoli SE, Sukhadia P, Mullaney KA, Gladdy R, et al. 2023.. Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: a clinicopathologic study of seven cases demonstrating a heterogenous entity. . Genes Chromosom. Cancer 62::191–201
     [Crossref] [Google Scholar]
  27. Dong J, Feldmann G, Huang J, Wu S, Zhang N, et al. 2007.. Elucidation of a universal size-control mechanism in Drosophila and mammals. . Cell 130::1120–33
     [Crossref] [Google Scholar]
  28. Doyle LA, Fletcher CD, Hornick JL. 2016.. Nuclear expression of CAMTA1 distinguishes epithelioid hemangioendothelioma from histologic mimics. . Am. J. Surg. Pathol. 40::94–102
     [Crossref] [Google Scholar]
  29. Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, et al. 2018.. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. . N. Engl. J. Med. 378::731–39
     [Crossref] [Google Scholar]
  30. Driskill JH, Pan D. 2021.. The Hippo pathway in liver homeostasis and pathophysiology. . Annu. Rev. Pathol. 16::299–322
     [Crossref] [Google Scholar]
  31. Driskill JH, Zheng Y, Wu B-K, Wang L, Cai J, et al. 2021.. WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma. . Genes Dev. 35::495–511
     [Crossref] [Google Scholar]
  32. Druker BJ. 2008.. Translation of the Philadelphia chromosome into therapy for CML. . Blood 112::4808–17
     [Crossref] [Google Scholar]
  33. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, et al. 2001a.. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. . N. Engl. J. Med. 344::1038–42
     [Crossref] [Google Scholar]
  34. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, et al. 2001b.. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. . N. Engl. J. Med. 344::1031–37
     [Crossref] [Google Scholar]
  35. Errani C, Zhang L, Sung YS, Hajdu M, Singer S, et al. 2011.. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. . Genes Chromosom. Cancer 50::644–53
     [Crossref] [Google Scholar]
  36. Flucke U, Vogels RJ, de Saint Aubain Somerhausen N, Creytens DH, Riedl RG, et al. 2014.. Epithelioid hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases. . Diagn. Pathol. 9::131
     [Crossref] [Google Scholar]
  37. Garcia K, Gingras AC, Harvey KF, Tanas MR. 2022.. TAZ/YAP fusion proteins: mechanistic insights and therapeutic opportunities. . Trends Cancer 8::1033–45
     [Crossref] [Google Scholar]
  38. Hagenbeek TJ, Webster JD, Kljavin NM, Chang MT, Pham T, et al. 2018.. The Hippo pathway effector TAZ induces TEAD-dependent liver inflammation and tumors. . Sci. Signal. 11::eaaj1757
     [Crossref] [Google Scholar]
  39. Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, et al. 2006.. The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. . Nat. Cell Biol. 8::27–36
     [Crossref] [Google Scholar]
  40. Henninger JE, Oksuz O, Shrinivas K, Sagi I, LeRoy G, et al. 2021.. RNA-mediated feedback control of transcriptional condensates. . Cell 184::207–25.e24
     [Crossref] [Google Scholar]
  41. Hu X, Wu X, Berry K, Zhao C, Xin D, et al. 2023.. Nuclear condensates of YAP fusion proteins alter transcription to drive ependymoma tumourigenesis. . Nat. Cell Biol. 25::323–36
     [Google Scholar]
  42. Isfort I, Cyra M, Elges S, Kailayangiri S, Altvater B, et al. 2019.. SS18-SSX-dependent YAP/TAZ signaling in synovial sarcoma. . Clin. Cancer Res. 25::3718–31
     [Crossref] [Google Scholar]
  43. Janse van Rensburg HJ, Azad T, Ling M, Hao Y, Snetsinger B, et al. 2018.. The Hippo pathway component TAZ promotes immune evasion in human cancer through PD-L1. . Cancer Res. 78::1457–70
     [Crossref] [Google Scholar]
  44. Ji J, Xu R, Zhang X, Han M, Xu Y, et al. 2018.. Actin like-6A promotes glioma progression through stabilization of transcriptional regulators YAP/TAZ. . Cell Death Dis. 9::517
     [Crossref] [Google Scholar]
  45. Jung R, Janardhan HP, Dresser K, Cotton JL, Hutchinson L, et al. 2021a.. Response by Jung et al to letter regarding article, “Sustained activation of endothelial YAP1 causes epithelioid hemangioendothelioma. .” Arterioscler. Thromb. Vasc. Biol. 41::e493–95
     [Google Scholar]
  46. Jung R, Janardhan HP, Dresser K, Cotton JL, Hutchinson L, et al. 2021b.. Sustained activation of endothelial YAP1 causes epithelioid hemangioendothelioma. . Arterioscler. Thromb. Vasc. Biol. 41::2233–35
     [Crossref] [Google Scholar]
  47. Kao Y-C, Lee J-C, Zhang L, Sung Y-S, Swanson D, et al. 2020.. Recurrent YAP1 and KMT2A gene rearrangements in a subset of MUC4-negative sclerosing epithelioid fibrosarcoma. . Am. J. Surg. Pathol. 44::368–77
     [Crossref] [Google Scholar]
  48. Kao Y-C, Sung Y-S, Zhang L, Chen C-L, Huang S-C, Antonescu CR. 2017.. Expanding the molecular signature of ossifying fibromyxoid tumors with two novel gene fusions: CREBBP-BCORL1 and KDM2A-WWTR1. . Genes Chromosom. Cancer 56::42–50
     [Crossref] [Google Scholar]
  49. Kapoor A, Yao W, Ying H, Hua S, Liewen A, et al. 2014.. Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer. . Cell 158::185–97
     [Crossref] [Google Scholar]
  50. Karajannis MA, Li BK, Souweidane MM, Liechty B, Yao J, et al. 2022.. YAP1-MAML2 fusion in a pediatric NF2-wildtype intraparenchymal brainstem schwannoma. . Acta Neuropathol. Commun. 10::117
     [Crossref] [Google Scholar]
  51. Khan AB, Gadot R, Shetty A, Bayley JC 5th, Hadley CC, et al. 2020.. Identification of novel fusion transcripts in meningioma. . J. Neurooncol. 149::219–30
     [Crossref] [Google Scholar]
  52. Koutlas IG, Oetting WS, Burns GM, Gopalakrishnan R, Antonescu CR. 2021.. Whole exome sequencing identifies somatic variants in an oral composite hemangioendothelioma characterized by YAP1-MAML2 fusion. . Head Neck Pathol. 16:(3):849–56
     [Crossref] [Google Scholar]
  53. Kupp R, Ruff L, Terranova S, Nathan E, Ballereau S, et al. 2021.. ZFTA translocations constitute ependymoma chromatin remodeling and transcription factors. . Cancer Discov. 11::2216–29
     [Crossref] [Google Scholar]
  54. Ladanyi M, Lui MY, Antonescu CR, Krause-Boehm A, Meindl A, et al. 2001.. The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. . Oncogene 20::48–57
     [Crossref] [Google Scholar]
  55. Lamar JM, Motilal Nehru V, Weinberg G. 2018.. Epithelioid hemangioendothelioma as a model of YAP/TAZ-driven cancer: insights from a rare fusion sarcoma. . Cancers 10::229
     [Crossref] [Google Scholar]
  56. Lei Q-Y, Zhang H, Zhao B, Zha Z-Y, Bai F, et al. 2008.. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the Hippo pathway. . Mol. Cell. Biol. 28::2426–36
     [Crossref] [Google Scholar]
  57. Li H, Li Q, Dang K, Ma S, Cotton JL, et al. 2019.. YAP/TAZ activation drives uveal melanoma initiation and progression. . Cell Rep. 29::3200–11.e4
     [Crossref] [Google Scholar]
  58. Lin JJ, Riely GJ, Shaw AT. 2017.. Targeting ALK: Precision medicine takes on drug resistance. . Cancer Discov. 7::137–55
     [Crossref] [Google Scholar]
  59. Lin L, Sabnis AJ, Chan E, Olivas V, Cade L, et al. 2015.. The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies. . Nat. Genet. 47::250–56
     [Crossref] [Google Scholar]
  60. Liu C-Y, Zha Z-Y, Zhou X, Zhang H, Huang W, et al. 2010.. The Hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCFβ-TrCP E3 ligase. . J. Biol. Chem. 285::37159–69
     [Crossref] [Google Scholar]
  61. Liu-Chittenden Y, Huang B, Shim JS, Chen Q, Lee SJ, et al. 2012.. Genetic and pharmacological disruption of the TEAD–YAP complex suppresses the oncogenic activity of YAP. . Genes Dev. 26::1300–5
     [Crossref] [Google Scholar]
  62. Long C, Grueter CE, Song K, Qin S, Qi X, et al. 2014.. Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor. . PNAS 111::11521–26
     [Crossref] [Google Scholar]
  63. Ma S, Kanai R, Pobbati AV, Li S, Che K, et al. 2022.. The TAZ-CAMTA1 fusion protein promotes tumorigenesis via connective tissue growth factor and Ras-MAPK signaling in epithelioid hemangioendothelioma. . Clin. Cancer Res. 28:(14):3116–26
     [Crossref] [Google Scholar]
  64. Ma S, Meng Z, Chen R, Guan KL. 2019.. The Hippo pathway: biology and pathophysiology. . Annu. Rev. Biochem. 88::577–604
     [Crossref] [Google Scholar]
  65. Merritt N, Garcia K, Rajendran D, Lin ZY, Zhang X, et al. 2021.. TAZ-CAMTA1 and YAP-TFE3 alter the TAZ/YAP transcriptome by recruiting the ATAC histone acetyltransferase complex. . eLife 10::e62857
     [Crossref] [Google Scholar]
  66. Mertens F, Johansson B, Fioretos T, Mitelman F. 2015.. The emerging complexity of gene fusions in cancer. . Nat. Rev. Cancer 15::371–81
     [Crossref] [Google Scholar]
  67. Mitelman F, Johansson B, Mertens F. 2007.. The impact of translocations and gene fusions on cancer causation. . Nat. Rev. Cancer 7::233–45
     [Crossref] [Google Scholar]
  68. Miyanaga A, Masuda M, Tsuta K, Kawasaki K, Nakamura Y, et al. 2015.. Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing. . J. Thorac. Oncol. 10::844–51
     [Crossref] [Google Scholar]
  69. Neto-Silva RM, de Beco S, Johnston LA. 2010.. Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. . Dev. Cell 19::507–20
     [Crossref] [Google Scholar]
  70. Nowell PC. 1962.. The minute chromosome (Phl) in chronic granulocytic leukemia. . Blut 8::65–66
     [Crossref] [Google Scholar]
  71. Ong YT, Andrade J, Armbruster M, Shi C, Castro M, et al. 2022.. A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth. . Nat. Metab. 4:(6):672–82
     [Crossref] [Google Scholar]
  72. Pajtler KW, Wei Y, Okonechnikov K, Silva PBG, Vouri M, et al. 2019.. YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis. . Nat. Commun. 10::3914
     [Crossref] [Google Scholar]
  73. Pajtler KW, Witt H, Sill M, Jones DT, Hovestadt V, et al. 2015.. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. . Cancer Cell 27::728–43
     [Crossref] [Google Scholar]
  74. Pan D. 2022.. The unfolding of the Hippo signaling pathway. . Dev. Biol. 487::1–9
     [Crossref] [Google Scholar]
  75. Panagopoulos I, Lobmaier I, Gorunova L, Heim S. 2019.. Fusion of the genes WWTR1 and FOSB in pseudomyogenic hemangioendothelioma. . Cancer Genom. Proteom. 16::293–98
     [Crossref] [Google Scholar]
  76. Park HW, Kim YC, Yu B, Moroishi T, Mo JS, et al. 2015.. Alternative Wnt signaling activates YAP/TAZ. . Cell 162::780–94
     [Crossref] [Google Scholar]
  77. Parker M, Mohankumar KM, Punchihewa C, Weinlich R, Dalton JD, et al. 2014.. C11orf95–RELA fusions drive oncogenic NF-κB signalling in ependymoma. . Nature 506::451–55
     [Crossref] [Google Scholar]
  78. Patel NR, Salim AA, Sayeed H, Sarabia SF, Hollingsworth F, et al. 2015.. Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants. . Histopathology 67::699–708
     [Crossref] [Google Scholar]
  79. Patton A, Bridge JA, Liebner D, Chung C, Iwenofu OH. 2022.. A YAP1::TFE3 cutaneous low-grade fibromyxoid neoplasm: a novel entity!. Genes Chromosom. Cancer 61::194–99
     [Crossref] [Google Scholar]
  80. Perret R, Tallegas M, Velasco V, Soubeyran I, Coindre JM, et al. 2022.. Recurrent YAP1::MAML2 fusions in “nodular necrotizing” variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases. . Modern Pathol. 35::1398–404
     [Crossref] [Google Scholar]
  81. Picco G, Chen ED, Alonso LG, Behan FM, Gonçalves E, et al. 2019.. Functional linkage of gene fusions to cancer cell fitness assessed by pharmacological and CRISPR-Cas9 screening. . Nat. Commun. 10::2198
     [Crossref] [Google Scholar]
  82. Piccolo S, Dupont S, Cordenonsi M. 2014.. The biology of YAP/TAZ: Hippo signaling and beyond. . Physiol. Rev. 94::1287–312
     [Crossref] [Google Scholar]
  83. Plouffe SW, Lin KC, Moore JL 3rd, Tan FE, Ma S, et al. 2018.. The Hippo pathway effector proteins YAP and TAZ have both distinct and overlapping functions in the cell. . J. Biol. Chem. 293::11230–40
     [Crossref] [Google Scholar]
  84. Pobbati AV, Han X, Hung AW, Weiguang S, Huda N, et al. 2015.. Targeting the central pocket in human transcription factor TEAD as a potential cancer therapeutic strategy. . Structure 23::2076–86
     [Crossref] [Google Scholar]
  85. Puls F, Agaimy A, Flucke U, Mentzel T, Sumathi VP, et al. 2020.. Recurrent fusions between YAP1 and KMT2A in morphologically distinct neoplasms within the spectrum of low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma. . Am. J. Surg. Pathol. 44::594–606
     [Crossref] [Google Scholar]
  86. Rosenbaum E, Jadeja B, Xu B, Zhang L, Agaram NP, et al. 2020.. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. . Modern Pathol. 33::591–602
     [Crossref] [Google Scholar]
  87. Sabari BR, Dall'Agnese A, Boija A, Klein IA, Coffey EL, et al. 2018.. Coactivator condensation at super-enhancers links phase separation and gene control. . Science 361::eaar3958
     [Crossref] [Google Scholar]
  88. Saleh AH, Samuel N, Juraschka K, Saleh MH, Taylor MD, Fehlings MG. 2022.. The biology of ependymomas and emerging novel therapies. . Nat. Rev. Cancer 22::208–22
     [Crossref] [Google Scholar]
  89. Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, et al. 2018.. Oncogenic signaling pathways in The Cancer Genome Atlas. . Cell 173::321–37.e10
     [Crossref] [Google Scholar]
  90. Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. 2014.. Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. . Oncol. Rev. 8::259
     [Google Scholar]
  91. Schieffer KM, Agarwal V, LaHaye S, Miller KE, Koboldt DC, et al. 2021.. YAP1-FAM118B fusion defines a rare subset of childhood and young adulthood meningiomas. . Am. J. Surg. Pathol. 45::329–40
     [Crossref] [Google Scholar]
  92. Schmelzle T, Chapeau E, Bauer D, Chene P, Faris J, et al. 2023.. IAG933, a selective and orally efficacious YAP1/WWTR1(TAZ)-panTEAD protein-protein interaction inhibitor with pre-clinical activity in monotherapy and combinations. . Cancer Res. 83::LB319
     [Crossref] [Google Scholar]
  93. Seavey CN, Hallett A, Li S, Che K, Pobbati AV, et al. 2023.. Loss of CDKN2A cooperates with WWTR1(TAZ)–CAMTA1 gene fusion to promote tumor progression in epithelioid hemangioendothelioma. . Clin. Cancer Res. 29:(13):2480–93
     [Crossref] [Google Scholar]
  94. Seavey CN, Pobbati AV, Hallett A, Ma S, Reynolds JP, et al. 2021.. WWTR1(TAZ)-CAMTA1 gene fusion is sufficient to dysregulate YAP/TAZ signaling and drive epithelioid hemangioendothelioma tumorigenesis. . Genes Dev. 35::512–27
     [Crossref] [Google Scholar]
  95. Seavey CN, Pobbati AV, Rubin BP. 2022.. Unraveling the biology of epithelioid hemangioendothelioma, a TAZ-CAMTA1 fusion driven sarcoma. . Cancers 14::2980
     [Crossref] [Google Scholar]
  96. Seavey CN, Rubin BP. 2021.. Letter by Seavey and Rubin regarding article, “Sustained activation of endothelial YAP1 causes epithelioid hemangioendothelioma. .” Arterioscler. Thromb. Vasc. Biol. 41::e491–92
     [Crossref] [Google Scholar]
  97. Sekine S, Kiyono T, Ryo E, Ogawa R, Wakai S, et al. 2019.. Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma. . J. Clin. Investig. 129::3827–32
     [Crossref] [Google Scholar]
  98. Seligson ND, Awasthi A, Millis SZ, Turpin BK, Meyer CF, et al. 2019.. Common secondary genomic variants associated with advanced epithelioid hemangioendothelioma. . JAMA Netw. Open 2::e1912416
     [Crossref] [Google Scholar]
  99. Shibuya R, Matsuyama A, Shiba E, Harada H, Yabuki K, Hisaoka M. 2015.. CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma. . Histopathology 67::827–35
     [Crossref] [Google Scholar]
  100. Shin Y, Brangwynne CP. 2017.. Liquid phase condensation in cell physiology and disease. . Science 357::eaaf4382
     [Crossref] [Google Scholar]
  101. Sievers P, Chiang J, Schrimpf D, Stichel D, Paramasivam N, et al. 2020.. YAP1-fusions in pediatric NF2-wildtype meningioma. . Acta Neuropathol. 139::215–18
     [Crossref] [Google Scholar]
  102. Stacchiotti S, Miah AB, Frezza AM, Messiou C, Morosi C, et al. 2021.. Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts. . ESMO Open 6::100170
     [Crossref] [Google Scholar]
  103. Subramaniam A, Zheng J, Yalamanchili S, Conley AP, Ratan R, et al. 2020.. Modulation of YAP/TAZ by statins to improve survival in epithelioid hemangioendothelioma (EHE). . J. Clin. Oncol. 38::e23527
     [Crossref] [Google Scholar]
  104. Suurmeijer AJH, Dickson BC, Swanson D, Sung YS, Zhang L, Antonescu CR. 2020.. Variant WWTR1 gene fusions in epithelioid hemangioendothelioma—a genetic subset associated with cardiac involvement. . Genes Chromosom. Cancer 59::389–95
     [Crossref] [Google Scholar]
  105. Szulzewsky F, Arora S, Arakaki A, Sievers P, Bonnin DAA, et al. 2022.. Both YAP1-MAML2 and constitutively active YAP1 drive the formation of tumors that resemble NF2-mutant meningiomas in mice. . Genes Dev. 36::857–70
     [Crossref] [Google Scholar]
  106. Szulzewsky F, Arora S, Hoellerbauer P, King C, Nathan E, et al. 2020.. Comparison of tumor-associated YAP1 fusions identifies a recurrent set of functions critical for oncogenesis. . Genes Dev. 34::1051–64
     [Crossref] [Google Scholar]
  107. Szulzewsky F, Holland EC, Vasioukhin V. 2021.. YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance. . Dev. Biol. 475::205–21
     [Crossref] [Google Scholar]
  108. Takadera M, Satomi K, Szulzewsky F, Cimino PJ, Holland EC, et al. 2020.. Phenotypic characterization with somatic genome editing and gene transfer reveals the diverse oncogenicity of ependymoma fusion genes. . Acta Neuropathol. Commun. 8::203
     [Crossref] [Google Scholar]
  109. Tanas MR, Ma S, Jadaan FO, Ng CK, Weigelt B, et al. 2016.. Mechanism of action of a WWTR1(TAZ)-CAMTA1 fusion oncoprotein. . Oncogene 35::929–38
     [Crossref] [Google Scholar]
  110. Tanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, et al. 2011.. Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. . Sci. Transl. Med. 3::98ra82
     [Crossref] [Google Scholar]
  111. Tang TT, Konradi AW, Feng Y, Peng X, Ma M, et al. 2021.. Small molecule inhibitors of TEAD auto-palmitoylation selectively inhibit proliferation and tumor growth of NF2-deficient mesothelioma. . Mol. Cancer Ther. 20::986–98
     [Crossref] [Google Scholar]
  112. Tolcher AW, Lakhani NJ, McKean M, Lingaraj T, Victor L, et al. 2022.. A phase 1, first-in-human study of IK-930, an oral TEAD inhibitor targeting the Hippo pathway in subjects with advanced solid tumors. . J. Clin. Oncol. 40::TPS3168
     [Crossref] [Google Scholar]
  113. Tonon G, Modi S, Wu L, Kubo A, Coxon AB, et al. 2003.. t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. . Nat. Genet. 33::208–13
     [Crossref] [Google Scholar]
  114. Trautmann M, Cheng YY, Jensen P, Azoitei N, Brunner I, et al. 2019.. Requirement for YAP1 signaling in myxoid liposarcoma. . EMBO Mol. Med. 11::e9889
     [Crossref] [Google Scholar]
  115. Tremblay AM, Missiaglia E, Galli GG, Hettmer S, Urcia R, et al. 2014.. The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation. . Cancer Cell 26::273–87
     [Crossref] [Google Scholar]
  116. Tsuda Y, Suurmeijer AJH, Sung Y-S, Zhang L, Healey JH, Antonescu CR. 2021.. Epithelioid hemangioma of bone harboring FOS and FOSB gene rearrangements: a clinicopathologic and molecular study. . Genes Chromosom. Cancer 60::17–25
     [Crossref] [Google Scholar]
  117. Valouev A, Weng Z, Sweeney RT, Varma S, Le QT, et al. 2014.. Discovery of recurrent structural variants in nasopharyngeal carcinoma. . Genome Res. 24::300–9
     [Crossref] [Google Scholar]
  118. Vivero M, Davineni P, Nardi V, Chan JKC, Sholl LM. 2020.. Metaplastic thymoma: a distinctive thymic neoplasm characterized by YAP1-MAML2 gene fusions. . Modern Pathol. 33::560–65
     [Crossref] [Google Scholar]
  119. Wang H, Lu B, Castillo J, Zhang Y, Yang Z, et al. 2016.. Tankyrase inhibitor sensitizes lung cancer cells to endothelial growth factor receptor (EGFR) inhibition via stabilizing angiomotins and inhibiting YAP signaling. . J. Biol. Chem. 291::15256–66
     [Crossref] [Google Scholar]
  120. Wang L, Choi K, Su T, Li B, Wu X, et al. 2022.. Multiphase coalescence mediates Hippo pathway activation. . Cell 185::4376–93.e18
     [Crossref] [Google Scholar]
  121. Wu L, Liu J, Gao P, Nakamura M, Cao Y, et al. 2005.. Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. . EMBO J. 24::2391–402
     [Crossref] [Google Scholar]
  122. Wu L, Sun T, Kobayashi K, Gao P, Griffin JD. 2002.. Identification of a family of mastermind-like transcriptional coactivators for mammalian Notch receptors. . Mol. Cell. Biol. 22::7688–700
     [Crossref] [Google Scholar]
  123. Wu LMN, Deng Y, Wang J, Zhao C, Wang J, et al. 2018.. Programming of Schwann cells by Lats1/2-TAZ/YAP signaling drives malignant peripheral nerve sheath tumorigenesis. . Cancer Cell 33::292–308.e7
     [Crossref] [Google Scholar]
  124. Yap TA, Kwiatkowski DJ, Desai J, Dagogo-Jack I, Millward M, et al. 2023.. First-in-class, first-in-human phase 1 trial of VT3989, an inhibitor of yes-associated protein (YAP)/transcriptional enhancer activator domain (TEAD), in patients (pts) with advanced solid tumors enriched for malignant mesothelioma and other tumors with neurofibromatosis 2 (NF2) mutations. . Cancer Res. 83::CT006
     [Crossref] [Google Scholar]
  125. Yimlamai D, Christodoulou C, Galli GG, Yanger K, Pepe-Mooney B, et al. 2014.. Hippo pathway activity influences liver cell fate. . Cell 157::1324–38
     [Crossref] [Google Scholar]
  126. Yin F, Yu J, Zheng Y, Chen Q, Zhang N, Pan D. 2013.. Spatial organization of Hippo signaling at the plasma membrane mediated by the tumor suppressor Merlin/NF2. . Cell 154::1342–55
     [Crossref] [Google Scholar]
  127. Zanconato F, Cordenonsi M, Piccolo S. 2016.. YAP/TAZ at the roots of cancer. . Cancer Cell 29::783–803
     [Crossref] [Google Scholar]
  128. Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, et al. 2015.. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. . Nat. Cell Biol. 17::1218–27
     [Crossref] [Google Scholar]
  129. Zhang N, Bai H, David KK, Dong J, Zheng Y, et al. 2010.. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. . Dev. Cell 19::27–38
     [Crossref] [Google Scholar]
  130. Zhao B, Li L, Lu Q, Wang LH, Liu CY, et al. 2011.. Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. . Genes Dev. 25::51–63
     [Crossref] [Google Scholar]
  131. Zhao B, Li L, Tumaneng K, Wang CY, Guan KL. 2010.. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCFβ-TRCP. . Genes Dev. 24::72–85
     [Crossref] [Google Scholar]
  132. Zhao B, Wei X, Li W, Udan RS, Yang Q, et al. 2007.. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. . Genes Dev. 21::2747–61
     [Crossref] [Google Scholar]
  133. Zhao B, Ye X, Yu J, Li L, Li W, et al. 2008.. TEAD mediates YAP-dependent gene induction and growth control. . Genes Dev. 22::1962–71
     [Crossref] [Google Scholar]
  134. Zhao J, Zhao R, Xiang C, Shao J, Guo L, Han Y. 2021.. YAP1-MAML2 fusion as a diagnostic biomarker for metaplastic thymoma. . Front. Oncol. 11::692283
     [Crossref] [Google Scholar]
  135. Zheng Y, Pan D. 2019.. The Hippo signaling pathway in development and disease. . Dev. Cell 50::264–82
     [Crossref] [Google Scholar]
  136. Zhou D, Conrad C, Xia F, Park JS, Payer B, et al. 2009.. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. . Cancer Cell 16::425–38
     [Crossref] [Google Scholar]
  137. Ziosi M, Baena-López LA, Grifoni D, Froldi F, Pession A, et al. 2010.. dMyc functions downstream of Yorkie to promote the supercompetitive behavior of Hippo pathway mutant cells. . PLOS Genet. 6::e1001140
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-061223-094639
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YAP, TAZ, and Hippo-Dysregulating Fusion Proteins in Cancer
Annual Review of Cancer Biology 8, 331 (2024); https://doi.org/10.1146/annurev-cancerbio-061223-094639
/content/journals/10.1146/annurev-cancerbio-061223-094639
/content/journals/10.1146/annurev-cancerbio-061223-094639
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