363
Views
0
CrossRef citations to date
0
Altmetric
Review

TACC3: a multi-functional protein promoting cancer cell survival and aggressiveness

& ORCID Icon
Pages 2637-2655 | Received 01 Nov 2023, Accepted 02 Jan 2024, Published online: 10 Jan 2024

References

  • Still IH, Vettaikkorumakankauv AK, DiMatteo A, et al. Structure-function evolution of the transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms. BMC Evol Biol. 2004;4(1):16. doi: 10.1186/1471-2148-4-16
  • Gergely F, Karlsson C, Still I, et al. The TACC domain identifies a family of centrosomal proteins that can interact with microtubules. Proc Natl Acad Sci U S A. 2000;97(26):14352–7. doi: 10.1073/pnas.97.26.14352
  • Gabillard JC, Ulisse S, Baldini E, et al. Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. Biochem Biophys Res Commun. 2011;408(4):647–53. doi: 10.1016/j.bbrc.2011.04.078
  • LeRoy PJ, Hunter JJ, Hoar KM, et al. Localization of human TACC3 to mitotic spindles is mediated by phosphorylation on Ser558 by Aurora A: a novel pharmacodynamic method for measuring Aurora a activity. Cancer Res. 2007;67(11):5362–70. doi: 10.1158/0008-5472.CAN-07-0122
  • Dou Z, Ding X, Zereshki A, et al. TTK kinase is essential for the centrosomal localization of TACC2. FEBS Lett. 2004;572(1–3):51–6. doi: 10.1016/j.febslet.2004.06.092
  • Tien AC, Lin MH, Su LJ, et al. Identification of the substrates and interaction proteins of aurora kinases from a protein-protein interaction model. Mol & Cell Proteomics. 2004;3(1):93–104. doi: 10.1074/mcp.M300072-MCP200
  • Ha GH, Kim JL, Breuer EK. Transforming acidic coiled-coil proteins (TACCs) in human cancer. Cancer Lett. 2013;336(1):24–33. doi: 10.1016/j.canlet.2013.04.022
  • Chen HM, Schmeichel KL, Mian IS, et al. AZU-1: a candidate breast tumor suppressor and biomarker for tumor progression. Mol Biol Cell. 2000;11(4):1357–67. doi: 10.1091/mbc.11.4.1357
  • Yoshida E, Terao Y, Hayashi N, et al. Promoter-level transcriptome in primary lesions of endometrial cancer identified biomarkers associated with lymph node metastasis. Sci Rep. 2017;7(1):14160. doi: 10.1038/s41598-017-14418-5
  • Angrisano T, Lembo F, Pero R, et al. TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters. Nucleic Acids Res. 2006;34(1):364–372. doi: 10.1093/nar/gkj400
  • Saatci O, Akbulut O, Cetin M, et al. Targeting TACC3 represents a novel vulnerability in highly aggressive breast cancers with centrosome amplification. Cell Death Differ. 2023;30(5):1305–1319. doi: 10.1038/s41418-023-01140-1
  • Ertych N, Bastians H. Interaction of TACC3 and TSC2 at the nuclear envelope and mitotic structures. Cell Cycle. 2010;9(7):1231–1240. doi: 10.4161/cc.9.7.11257
  • Gomez-Baldo L, Schmidt S, Maxwell CA, et al. TACC3-TSC2 maintains nuclear envelope structure and controls cell division. Cell Cycle. 2010;9(6):1143–55. doi: 10.4161/cc.9.6.11018
  • Thakur HC, Singh M, Nagel-Steger L, et al. The centrosomal adaptor TACC3 and the microtubule polymerase chTOG interact via defined C-terminal subdomains in an aurora-A kinase-independent manner. J Biol Chem. 2014;289(1):74–88. doi: 10.1074/jbc.M113.532333
  • Still IH, Hamilton M, Vince P, et al. Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. Oncogene. 1999;18(27):4032–8. doi: 10.1038/sj.onc.1202801
  • Still IH, Vince P, Cowell JK. The third member of the transforming acidic coiled coil-containing gene family, TACC3, maps in 4p16, close to translocation breakpoints in multiple myeloma, and is upregulated in various cancer cell lines. Genomics. 1999;58(2):165–70. doi: 10.1006/geno.1999.5829
  • Adnane J, Gaudray P, Dionne CA, et al. BEK and FLG, two receptors to members of the FGF family, are amplified in subsets of human breast cancers. Oncogene. 1991;6(4):659–663.
  • Kiemeney LA, Sulem P, Besenbacher S, et al. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nat Genet. 2010;42(5):415–9. doi: 10.1038/ng.558
  • Piekorz RP, Hoffmeyer A, Duntsch CD, et al. The centrosomal protein TACC3 is essential for hematopoietic stem cell function and genetically interfaces with p53-regulated apoptosis. EMBO J. 2002;21(4):653–664. doi: 10.1093/emboj/21.4.653
  • Sadek CM, Pelto-Huikko M, Tujague M, et al. TACC3 expression is tightly regulated during early differentiation. Gene Expr Patterns. 2003;3(2):203–211. doi: 10.1016/s1567-133x(02)00066-2
  • Conte N, Charafe-Jauffret E, Delaval B, et al. Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. Oncogene. 2002;21(36):5619–30. doi: 10.1038/sj.onc.1205658
  • Cully M, Shiu J, Piekorz RP, et al. Transforming acidic coiled coil 1 promotes transformation and mammary tumorigenesis. Cancer Res. 2005;65(22):10363–70. doi: 10.1158/0008-5472.CAN-05-1633
  • Schuendeln MM, Piekorz RP, Wichmann C, et al. The centrosomal, putative tumor suppressor protein TACC2 is dispensable for normal development, and deficiency does not lead to cancer. Mol Cell Biol. 2004;24(14):6403–9. doi: 10.1128/MCB.24.14.6403-6409.2004
  • Lauffart B, Gangisetty O, Still IH. Molecular cloning, genomic structure and interactions of the putative breast tumor suppressor TACC2. Genomics. 2003;81(2):192–201. doi: 10.1016/s0888-7543(02)00039-3
  • Cheng S, Douglas-Jones A, Yang X, et al. Transforming acidic coiled-coil-containing protein 2 (TACC2) in human breast cancer, expression pattern and clinical/prognostic relevance. Cancer Genomics Proteomics. 2010;7:67–73. doi: 10.1158/0008-5472.SABCS-09-3159
  • Takayama K, Horie-Inoue K, Suzuki T, et al. TACC2 is an androgen-responsive cell cycle regulator promoting androgen-mediated and castration-resistant growth of prostate cancer. Mol Endocrinol. 2012;26(5):748–61. doi: 10.1210/me.2011-1242
  • Song H, Liu C, Shen N, et al. Overexpression of TACC3 in breast cancer associates with poor prognosis. Appl Immunohistochem Mol Morphol. 2018;26(2):113–119. doi: 10.1097/PAI.0000000000000392
  • Li Q, Ye L, Guo W, et al. Overexpression of TACC3 is correlated with tumor aggressiveness and poor prognosis in prostate cancer. Biochem Biophys Res Commun. 2017;486(4):872–878. doi: 10.1016/j.bbrc.2017.03.090
  • Du Y, Liu L, Wang C, et al. TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis. Oncotarget. 2016;7:41885–41897. doi: 10.18632/oncotarget.9628
  • Yun M, Rong J, Lin ZR, et al. High expression of transforming acidic coiled coil-containing protein 3 strongly correlates with aggressive characteristics and poor prognosis of gastric cancer. Oncol Rep. 2015;34(3):1397–405. doi: 10.3892/or.2015.4093
  • Fang Z, Lin M, Chen S, et al. E2F1 promotes cell cycle progression by stabilizing spindle fiber in colorectal cancer cells. Cell Mol Biol Lett. 2022;27(1):90. doi: 10.1186/s11658-022-00392-y
  • Sabat-Pospiech D, Fabian-Kolpanowicz K, Prior IA, et al. Targeting centrosome amplification, an achilles’ heel of cancer. Biochem Soc Trans. 2019;47(5):1209–1222. doi: 10.1042/BST20190034
  • Partch CL, Gardner KH. Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B. Proc Natl Acad Sci U S A. 2011;108(19):7739–44. doi: 10.1073/pnas.1101357108
  • Fan Y, Zhou L, Pan L. Tumor-augmenting effect of histone methyltransferase WHSC1 on colorectal cancer via epigenetic upregulation of TACC3 and PI3K/Akt activation. Arch Med Res. 2022;53(7):658–665. doi: 10.1016/j.arcmed.2022.10.006
  • Shen C, Sheng Y, Zhu AC, et al. RNA demethylase ALKBH5 selectively promotes tumorigenesis and cancer stem cell self-renewal in acute myeloid leukemia. Cell Stem Cell. 2020;27(1):64–80.e9. doi: 10.1016/j.stem.2020.04.009
  • Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet. 2011;12(2):99–110. doi: 10.1038/nrg2936
  • Rio-Machin A, Ferreira BI, Henry T, et al. Downregulation of specific miRnas in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype. Leukemia. 2013;27(4):925–31. doi: 10.1038/leu.2012.302
  • Sun Y, Tian Y, Wang GZ, et al. Overexpression of transforming acidic coiled coil‑containing protein 3 reflects malignant characteristics and poor prognosis of glioma. Int J Mol Sci. 2017;18(3):235. doi: 10.3390/ijms18030235
  • Helsten T, Elkin S, Arthur E, et al. The FGFR Landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res. 2016;22(1):259–67. doi: 10.1158/1078-0432.CCR-14-3212
  • Parker BC, Annala MJ, Cogdell DE, et al. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J Clin Invest. 2013;123:855–65. doi: 10.1172/JCI67144
  • Charrasse S, Schroeder M, Gauthier-Rouviere C, et al. The TOGp protein is a new human microtubule-associated protein homologous to the xenopus XMAP215. J Cell Sci. 1998;111(Pt 10):1371–1383. doi: 10.1242/jcs.111.10.1371
  • Royle SJ, Bright NA, Lagnado L. Clathrin is required for the function of the mitotic spindle. Nature. 2005;434(7037):1152–7. doi: 10.1038/nature03502
  • Nixon FM, Gutierrez-Caballero C, Hood FE, et al. The mesh is a network of microtubule connectors that stabilizes individual kinetochore fibers of the mitotic spindle. Elife. 2015;4. doi: 10.7554/eLife.07635
  • Booth DG, Hood FE, Prior IA, et al. A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging. EMBO J. 2011;30(5):906–19. doi: 10.1038/emboj.2011.15
  • Fu W, Tao W, Zheng P, et al. Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment. J Cell Sci. 2010;123(21):3645–51. doi: 10.1242/jcs.075911
  • Hubner NC, Bird AW, Cox J, et al. Quantitative proteomics combined with BAC TransgeneOmics reveals in vivo protein interactions. J Cell Bio. 2010;189(4):739–54. doi: 10.1083/jcb.200911091
  • Lin CH, Hu CK, Shih HM. Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability. J Cell Bio. 2010;189(7):1097–105. doi: 10.1083/jcb.200911120
  • Ma MP, Robinson PJ, Chircop M. Sorting nexin 9 recruits clathrin heavy chain to the mitotic spindle for chromosome alignment and segregation. PLoS One. 2013;8(7):e68387. doi: 10.1371/journal.pone.0068387
  • Yamauchi T, Ishidao T, Nomura T, et al. A B-Myb complex containing clathrin and filamin is required for mitotic spindle function. EMBO J. 2008;27(13):1852–1862. doi: 10.1038/emboj.2008.118
  • Shimizu H, Nagamori I, Yabuta N, et al. GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression. J Cell Sci. 2009;122(17):3145–52. doi: 10.1242/jcs.052795
  • Hood FE, Williams SJ, Burgess SG, et al. Coordination of adjacent domains mediates TACC3–ch-TOG–clathrin assembly and mitotic spindle binding. J Cell Bio. 2013;202(3):463–478. doi: 10.1083/jcb.201211127
  • Gard DL, Kirschner MW. A microtubule-associated protein from xenopus eggs that specifically promotes assembly at the plus-end. J Cell Bio. 1987;105(5):2203–15. doi: 10.1083/jcb.105.5.2203
  • Burgess SG, Peset I, Joseph N, et al. Aurora-A-Dependent control of TACC3 influences the rate of mitotic spindle assembly. PLoS Genet. 2015;11(7):e1005345. doi: 10.1371/journal.pgen.1005345
  • Gulluni F, Martini M, De Santis MC, et al. Mitotic spindle assembly and genomic stability in breast cancer require PI3K-C2α scaffolding function. Cancer Cell. 2017;32(4):444–459.e7. doi: 10.1016/j.ccell.2017.09.002
  • Ryan EL, Shelford J, Massam-Wu T, et al. Defining endogenous TACC3–chTOG–clathrin–GTSE1 interactions at the mitotic spindle using induced relocalization. J Cell Sci. 2021;134(3). doi: 10.1242/jcs.255794
  • Liu A, Zeng S, Lu X, et al. Overexpression of G2 and S phase-expressed-1 contributes to cell proliferation, migration, and invasion via regulating p53/FoxM1/CCNB1 pathway and predicts poor prognosis in bladder cancer. Int J Biol Macromol. 2019;123:322–334. doi: 10.1016/j.ijbiomac.2018.11.032
  • Subhash VV, Tan SH, Tan WL, et al. GTSE1 expression represses apoptotic signaling and confers cisplatin resistance in gastric cancer cells. BMC Cancer. 2015;15(1):550. doi: 10.1186/s12885-015-1550-0
  • Nwagbara BU, Faris AE, Bearce EA, et al. TACC3 is a microtubule plus end–tracking protein that promotes axon elongation and also regulates microtubule plus end dynamics in multiple embryonic cell types. Mol Biol Cell. 2014;25(21):3350–3362. doi: 10.1091/mbc.E14-06-1121
  • Gutierrez-Caballero C, Burgess SG, Bayliss R, et al. TACC3–ch-TOG track the growing tips of microtubules independently of clathrin and aurora-A phosphorylation. Biol Open. 2015;4(2):170–179. doi: 10.1242/bio.201410843
  • Fu W, Chen H, Wang G, et al. Self-assembly and sorting of acentrosomal microtubules by TACC3 facilitate kinetochore capture during the mitotic spindle assembly. Proc Natl Acad Sci U S A. 2013;110(38):15295–300. doi: 10.1073/pnas.1312382110
  • Gergely F, Draviam VM, Raff JW. The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells. Genes Dev. 2003;17(3):336–41. doi: 10.1101/gad.245603
  • Rajeev R, Mukhopadhyay S, Bhagyanath S, et al. TACC3–ch-TOG interaction regulates spindle microtubule assembly by controlling centrosomal recruitment of γ-TuRC. Biosci Rep. 2023;43(3). doi: 10.1042/BSR20221882
  • Barros TP, Kinoshita K, Hyman AA, et al. Aurora A activates D-TACC–Msps complexes exclusively at centrosomes to stabilize centrosomal microtubules. J Cell Bio. 2005;170(7):1039–1046. doi: 10.1083/jcb.200504097
  • Kinoshita K, Noetzel TL, Pelletier L, et al. Aurora a phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis. J Cell Bio. 2005;170(7):1047–55. doi: 10.1083/jcb.200503023
  • Foraker AB, Camus SM, Evans TM, et al. Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG. J Cell Bio. 2012;198(4):591–605. doi: 10.1083/jcb.201205116
  • Singh P, Thomas GE, Gireesh KK, et al. TACC3 protein regulates microtubule nucleation by affecting γ-tubulin ring complexes. J Biol Chem. 2014;289(46):31719–31735. doi: 10.1074/jbc.M114.575100
  • Akbulut O, Lengerli D, Saatci O, et al. A highly potent TACC3 inhibitor as a novel anticancer drug candidate. Mol Cancer Ther. 2020;19(6):1243–1254. doi: 10.1158/1535-7163.MCT-19-0957
  • Rajeev R, Singh P, Asmita A, et al. Aurora a site specific TACC3 phosphorylation regulates astral microtubule assembly by stabilizing γ-tubulin ring complex. BMC Mol Cell Biol. 2019;20(1):58. doi: 10.1186/s12860-019-0242-z
  • Mori D, Yano Y, Toyo-Oka K, et al. NDEL1 phosphorylation by aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment. Mol Cell Biol. 2007;27(1):352–67. doi: 10.1128/MCB.00878-06
  • Godinho SA, Pellman D. Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Sci. 2014;369(1650):20130467. doi: 10.1098/rstb.2013.0467
  • Fukasawa K, Choi T, Kuriyama R, et al. Abnormal centrosome amplification in the absence of p53. Science. 1996;271(5256):1744–7. doi: 10.1126/science.271.5256.1744
  • Pannu V, Mittal K, Cantuaria G, et al. Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers. Oncotarget. 2015;6(12):10487–97. doi: 10.18632/oncotarget.3402
  • Gergely F, Basto R. Multiple centrosomes: together they stand, divided they fall. Genes Dev. 2008;22(17):2291–6. doi: 10.1101/gad.1715208
  • Fielding AB, Lim S, Montgomery K, et al. A critical role of integrin-linked kinase, ch-TOG and TACC3 in centrosome clustering in cancer cells. Oncogene. 2011;30(5):521–34. doi: 10.1038/onc.2010.431
  • Sadek CM, Jalaguier S, Feeney EP, et al. Isolation and characterization of AINT: a novel ARNT interacting protein expressed during murine embryonic development. Mech Dev. 2000;97(1–2):13–26. doi: 10.1016/s0925-4773(00)00415-9
  • Wang GL, Jiang BH, Rue EA, et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92(12):5510–4. doi: 10.1073/pnas.92.12.5510
  • Guo Y, Partch CL, Key J, et al. Regulating the ARNT/TACC3 axis: multiple approaches to manipulating protein/protein interactions with small molecules. ACS Chem Biol. 2013;8(3):626–35. doi: 10.1021/cb300604u
  • Harris AL. Hypoxia — a key regulatory factor in tumour growth. Nat Rev Cancer. 2002;2(1):38–47. doi: 10.1038/nrc704
  • Simpson RJ, Yi Lee SH, Bartle N, et al. A classic zinc finger from friend of GATA mediates an interaction with the coiled-coil of transforming acidic coiled-coil 3. J Biol Chem. 2004;279(38):39789–39797. doi: 10.1074/jbc.M404130200
  • Garriga-Canut M, Orkin SH. Transforming acidic coiled-coil protein 3 (TACC3) controls friend of GATA-1 (FOG-1) subcellular localization and regulates the association between GATA-1 and FOG-1 during hematopoiesis. J Biol Chem. 2004;279(22):23597–605. doi: 10.1074/jbc.M313987200
  • Tsang AP, Visvader JE, Turner CA, et al. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell. 1997;90(1):109–119. doi: 10.1016/S0092-8674(00)80318-9
  • Wang X, Crispino JD, Letting DL, et al. Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors. EMBO J. 2002;21(19):5225–34. doi: 10.1093/emboj/cdf527
  • Zheng R, Blobel GA. GATA transcription factors and cancer. Genes Cancer. 2010;1(12):1178–88. doi: 10.1177/1947601911404223
  • He JC, Yao W, Wang JM, et al. TACC3 overexpression in cholangiocarcinoma correlates with poor prognosis and is a potential anti-cancer molecular drug target for HDAC inhibitors. Oncotarget. 2016;7(46):75441–75456. doi: 10.18632/oncotarget.12254
  • Wen YL, Yan SM, Wei W, et al. Transforming acidic coiled-coil protein-3: a novel marker for differential diagnosis and prognosis prediction in endocervical adenocarcinoma. Mol Med. 2021;27(1):60. doi: 10.1186/s10020-021-00298-z
  • Lauffart B, Vaughan MM, Eddy R, et al. Aberrations of TACC1 and TACC3 are associated with ovarian cancer. BMC Womens Health. 2005;5(1):8. doi: 10.1186/1472-6874-5-8
  • Jiang F, Kuang B, Que Y, et al. The clinical significance of transforming acidic coiled-coil protein 3 expression in non-small cell lung cancer. Oncol Rep. 2016;35(1):436–46. doi: 10.3892/or.2015.4373
  • Jung CK, Jung JH, Park GS, et al. Expression of transforming acidic coiled-coil containing protein 3 is a novel independent prognostic marker in non-small cell lung cancer. Pathol Int. 2006;56(9):503–9. doi: 10.1111/j.1440-1827.2006.01998.x
  • Fan X, Liu B, Wang Z, et al. TACC3 is a prognostic biomarker for kidney renal clear cell carcinoma and correlates with immune cell infiltration and T cell exhaustion. Aging. 2021;13(6):8541–8562. doi: 10.18632/aging.202668
  • Matsuda K, Miyoshi H, Hiraoka K, et al. Elevated expression of transforming acidic coiled-coil containing protein 3 (TACC3) is associated with a poor prognosis in osteosarcoma. Clin Orthop Relat Res. 2018;476(9):1848–1855. doi: 10.1097/CORR.0000000000000379
  • Huang ZL, Lin ZR, Xiao YR, et al. High expression of TACC3 in esophageal squamous cell carcinoma correlates with poor prognosis. Oncotarget. 2015;6(9):6850–61. doi: 10.18632/oncotarget.3190
  • Zhou DS, Wang HB, Zhou ZG, et al. TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma. Oncotarget. 2015;6(27):24163–77. doi: 10.18632/oncotarget.4643
  • Moritsubo M, Miyoshi H, Matsuda K, et al. TACC3 expression as a prognostic factor in aggressive types of adult T-cell leukemia/lymphoma patients. Int J Lab Hematol. 2020;42(6):842–848. doi: 10.1111/ijlh.13289
  • Singh D, Chan JM, Zoppoli P, et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 2012;337(6099):1231–5. doi: 10.1126/science.1220834
  • Koutros S, Kiemeney LA, Pal Choudhury P, et al. Genome-wide association study of bladder cancer reveals new biological and translational insights. Eur Urol. 2023;84(1):127–137. doi: 10.1016/j.eururo.2023.04.020
  • Capelletti M, Dodge ME, Ercan D, et al. Identification of recurrent FGFR3–TACC3 fusion oncogenes from lung adenocarcinoma. Clin Cancer Res. 2014;20(24):6551–6558. doi: 10.1158/1078-0432.CCR-14-1337
  • Tamura R, Yoshihara K, Saito T, et al. Novel therapeutic strategy for cervical cancer harboring FGFR3-TACC3 fusions. Oncogenesis. 2018;7(1):4. doi: 10.1038/s41389-017-0018-2
  • Chew NJ, Nguyen EV, Su SP, et al. FGFR3 signaling and function in triple negative breast cancer. Cell Commun Signal. 2020;18(1):13. doi: 10.1186/s12964-019-0486-4
  • Bielle F, Di Stefano AL, Meyronet D, et al. Diffuse gliomas with FGFR3-TACC3 fusion have characteristic histopathological and molecular features. Brain Pathol. 2018;28(5):674–683. doi: 10.1111/bpa.12563
  • Kurobe M, Kojima T, Nishimura K, et al. Development of RNA-FISH assay for detection of oncogenic FGFR3-TACC3 fusion genes in FFPE samples. PloS One. 2016;11(12):e0165109. doi: 10.1371/journal.pone.0165109
  • Haura EB, Hicks JK, Boyle TA. erdafitinib overcomes FGFR3-TACC3–mediated resistance to osimertinib. J Thorac Oncol. 2020;15(9):e154–e156. doi: 10.1016/j.jtho.2019.12.132
  • Ou SI, Horn L, Cruz M, et al. Emergence of FGFR3-TACC3 fusions as a potential by-pass resistance mechanism to EGFR tyrosine kinase inhibitors in EGFR mutated NSCLC patients. Lung Cancer. 2017;111:61–64. doi: 10.1016/j.lungcan.2017.07.006
  • Raphael A, Dudnik E, Hershkovitz D, et al. FGFR fusions as an acquired resistance mechanism following treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) and a suggested novel target in advanced non-small cell lung cancer (aNSCLC). J Clin Med. 2022;11(9):2475. doi: 10.3390/jcm11092475
  • Di Stefano AL, Picca A, Saragoussi E, et al. Clinical, molecular, and radiomic profile of gliomas with FGFR3-TACC3 fusions. Neuro Oncol. 2020;22(11):1614–1624. doi: 10.1093/neuonc/noaa121
  • Nobusawa S, Watanabe T, Kleihues P, et al. IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res. 2009;15(19):6002–7. doi: 10.1158/1078-0432.CCR-09-0715
  • Suhail TV, Singh P, Manna TK. Suppression of centrosome protein TACC3 induces G1 arrest and cell death through activation of p38–p53–p21 stress signaling pathway. Eur J Cell Biol. 2015;94(2):90–100. doi: 10.1016/j.ejcb.2014.12.001
  • Ha GH, Park JS, Breuer EK. TACC3 promotes epithelial–mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways. Cancer Lett. 2013;332(1):63–73. doi: 10.1016/j.canlet.2013.01.013
  • Yao R, Natsume Y, Saiki Y, et al. Disruption of Tacc3 function leads to in vivo tumor regression. Oncogene. 2012;31:135–148. doi: 10.1038/onc.2011.235
  • Wurdak H, Zhu S, Min KH, et al. A small molecule accelerates neuronal differentiation in the adult rat. Proc Natl Acad Sci U S A. 2010;107(38):16542–7. doi: 10.1073/pnas.1010300107
  • Campo L, Breuer EK. Inhibition of TACC3 by a small molecule inhibitor in breast cancer. Biochem Biophys Res Commun. 2018;498(4):1085–1092. doi: 10.1016/j.bbrc.2018.03.125
  • Polson ES, Kuchler VB, Abbosh C, et al. KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice. Sci Transl Med. 2018;10(454). doi: 10.1126/scitranslmed.aar2718
  • Yao R, Kondoh Y, Natsume Y, et al. A small compound targeting TACC3 revealed its different spatiotemporal contributions for spindle assembly in cancer cells. Oncogene. 2014;33(33):4242–4252. doi: 10.1038/onc.2013.382
  • Ohoka N, Nagai K, Hattori T, et al. Cancer cell death induced by novel small molecules degrading the TACC3 protein via the ubiquitin–proteasome pathway. Cell Death Dis. 2014;5(11):e1513. doi: 10.1038/cddis.2014.471
  • Schmidt S, Schneider L, Essmann F, et al. The centrosomal protein TACC3 controls paclitaxel sensitivity by modulating a premature senescence program. Oncogene. 2010;29(46):6184–92. doi: 10.1038/onc.2010.354
  • Yim EK, Tong SY, Ho EM, et al. Anticancer effects on TACC3 by treatment of paclitaxel in HPV-18 positive cervical carcinoma cells. Oncol Rep. 2009;21(2):549–557.
  • Ohoka N, Nagai K, Shibata N, et al. SNIPER(TACC3) induces cytoplasmic vacuolization and sensitizes cancer cells to Bortezomib. Cancer Sci. 2017;108(5):1032–1041. doi: 10.1111/cas.13198
  • Gedik ME, Saatci O, Oberholtzer N, et al. Reviving immunogenic cell death upon targeting TACC3 enhances T-DM1 response in HER2-positive breast cancer. bioRxiv. 2023. doi: 10.1101/2023.09.12.557273
  • Nelson KN, Meyer AN, Wang CG, et al. Oncogenic driver FGFR3-TACC3 is dependent on membrane trafficking and ERK signaling. Oncotarget. 2018;9(76):34306–34319. doi: 10.18632/oncotarget.26142
  • Nelson KN, Meyer AN, Siari A, et al. Oncogenic gene fusion FGFR3-TACC3 is regulated by tyrosine phosphorylation. Mol Cancer Res. 2016;14(5):458–69. doi: 10.1158/1541-7786.MCR-15-0497
  • Weickhardt AJ, Lau DK, Hodgson-Garms M, et al. Dual targeting of FGFR3 and ERBB3 enhances the efficacy of FGFR inhibitors in FGFR3 fusion-driven bladder cancer. BMC Cancer. 2022;22(1):478. doi: 10.1186/s12885-022-09478-4
  • Parker Kerrigan BC, Ledbetter D, Kronowitz M, et al. RNAi technology targeting the FGFR3-TACC3 fusion breakpoint: an opportunity for precision medicine. Neurooncol Adv. 2020;2(1):vdaa132. doi: 10.1093/noajnl/vdaa132
  • Li T, Mehraein-Ghomi F, Forbes ME, et al. HSP90-CDC37 functions as a chaperone for the oncogenic FGFR3-TACC3 fusion. Mol Ther. 2022;30(4):1610–1627. doi: 10.1016/j.ymthe.2022.02.009

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.