High expression of transforming acidic coiled coil-containing protein 3 strongly correlates with aggressive characteristics and poor prognosis of gastric cancer

Yun,Miao; Rong,Jian; Lin,Zhi-Rui; He,Yu-Long; Zhang,Jia-Xing; Peng,Zhen-Wei; Tang,Lin-Quan; Zeng,Mu-Sheng; Zhong,Qian; Ye,Sheng

doi:10.3892/or.2015.4093

High expression of transforming acidic coiled coil-containing protein 3 strongly correlates with aggressive characteristics and poor prognosis of gastric cancer

Authors:
- Miao Yun
- Jian Rong
- Zhi-Rui Lin
- Yu-Long He
- Jia-Xing Zhang
- Zhen-Wei Peng
- Lin-Quan Tang
- Mu-Sheng Zeng
- Qian Zhong
- Sheng Ye
View Affiliations

Affiliations: Department of Oncology, The First Afﬁliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China, Department of Extracorporeal Circulation, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat‑sen University Cancer Center, Guangzhou, Guangdong, P.R. China, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China
Published online on: June 30, 2015 https://doi.org/10.3892/or.2015.4093
Pages: 1397-1405

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Transforming acidic coiled coil-containing protein 3 (TACC3) is well understood to regulate mitotic spindle dynamics and centrosome integrity during mitosis. TACC3 has been suggested to be deregulated in a variety of human malignancies and may be involved in the process of cancer progression. The aim of the present study was to determine the status of TACC3 expression in gastric cancer (GC) and to clarify its clinical/prognostic significance. In the present study, we applied quantitative PCR (qPCR) and western blotting to examine TACC3 mRNA/protein expression in paired GC tissues and matched adjacent non-malignant tissues. Immunohistochemistry (IHC) was performed on a large cohort of 186 postoperative GC samples. Chi-square test, Kaplan-Meier analysis and Cox regression modelling were used to analyse the data. Upregulated mRNA and protein expression levels of TACC3 were observed in the majority of the GC tissues based on qPCR and western blotting compared to the adjacent non-cancerous gastric tissues. Specific IHC staining for TACC3 was predominantly identified in the cytoplasm of the cancer cells. A high expression of TACC3 was detected in 102 of the 186 (54.8%) tissue samples and was significantly associated with the extracapsular extension of the tumour (P<0.001), tumour relapse (P<0.001) and shortened overall survival in GC (P<0.001). Further analysis demonstrated that the TACC3 expression level stratified the patient outcome in stage II (P=0.040), stage III (P<0.001), T3/4 (P<0.001), N positive (P<0.001) and poorly differentiated/undifferentiated tumour subgroups (P<0.001). The Cox regression analysis suggested that a high expression of TACC3 was an independent prognostic factor for GC patients. The measurement of TACC3 protein expression may be beneficial for predicting clinical outcomes for GC patients.

View Figures

View References

1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Theuer CP, Kurosaki T, Ziogas A, Butler J and Anton-Culver H: Asian patients with gastric carcinoma in the United States exhibit unique clinical features and superior overall and cancer specific survival rates. Cancer. 89:1883–1892. 2000. View Article : Google Scholar : PubMed/NCBI
3	Sasako M, Inoue M, Lin JT, Khor C, Yang HK and Ohtsu A: Gastric Cancer Working Group report. Jpn J Clin Oncol. 40(Suppl 1): i28–i37. 2010. View Article : Google Scholar : PubMed/NCBI
4	Kellogg DR, Moritz M and Alberts BM: The centrosome and cellular organization. Annu Rev Biochem. 63:639–674. 1994. View Article : Google Scholar : PubMed/NCBI
5	Pihan GA and Doxsey SJ: The mitotic machinery as a source of genetic instability in cancer. Semin Cancer Biol. 9:289–302. 1999. View Article : Google Scholar : PubMed/NCBI
6	Sen S: Aneuploidy and cancer. Curr Opin Oncol. 12:82–88. 2000. View Article : Google Scholar : PubMed/NCBI
7	Sánchez-Pérez I, García Alonso P and Belda Iniesta C: Clinical impact of aneuploidy on gastric cancer patients. Clin Transl Oncol. 11:493–498. 2009. View Article : Google Scholar : PubMed/NCBI
8	Gómez-Baldó L, Schmidt S, Maxwell CA, Bonifaci N, Gabaldón T, Vidalain PO, Senapedis W, Kletke A, Rosing M, Barnekow A, et al: TACC3-TSC2 maintains nuclear envelope structure and controls cell division. Cell Cycle. 9:1143–1155. 2010. View Article : Google Scholar : PubMed/NCBI
9	Albee AJ and Wiese C: Xenopus TACC3/maskin is not required for microtubule stability but is required for anchoring microtubules at the centrosome. Mol Biol Cell. 19:3347–3356. 2008. View Article : Google Scholar : PubMed/NCBI
10	Peset I and Vernos I: The TACC proteins: TACC-ling microtubule dynamics and centrosome function. Trends Cell Biol. 18:379–388. 2008. View Article : Google Scholar : PubMed/NCBI
11	Yao R, Natsume Y and Noda T: TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton. Cancer Sci. 98:555–562. 2007. View Article : Google Scholar : PubMed/NCBI
12	Schneider L, Essmann F, Kletke A, Rio P, Hanenberg H, Wetzel W, Schulze-Osthoff K, Nürnberg B and Piekorz RP: The transforming acidic coiled coil 3 protein is essential for spindle-dependent chromosome alignment and mitotic survival. J Biol Chem. 282:29273–29283. 2007. View Article : Google Scholar : PubMed/NCBI
13	Kinoshita K, Noetzel TL, Pelletier L, Mechtler K, Drechsel DN, Schwager A, Lee M, Raff JW and Hyman AA: Aurora A phosphorylation of TACC3/maskin is required for centrosome-dependent microtubule assembly in mitosis. J Cell Biol. 170:1047–1055. 2005. View Article : Google Scholar : PubMed/NCBI
14	Gergely F, Draviam VM and Raff JW: The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells. Genes Dev. 17:336–341. 2003. View Article : Google Scholar : PubMed/NCBI
15	Gergely F, Karlsson C, Still I, Cowell J, Kilmartin J and Raff JW: The TACC domain identifies a family of centrosomal proteins that can interact with microtubules. Proc Natl Acad Sci USA. 97:14352–14357. 2000. View Article : Google Scholar : PubMed/NCBI
16	Ha GH, Kim JL and Breuer EK: Transforming acidic coiled-coil proteins (TACCs) in human cancer. Cancer Lett. 336:24–33. 2013. View Article : Google Scholar : PubMed/NCBI
17	L'Espérance S, Popa I, Bachvarova M, Plante M, Patten N, Wu L, Têtu B and Bachvarov D: Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: Molecular signatures of chemoresistant tumors. Int J Oncol. 29:5–24. 2006.PubMed/NCBI
18	Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P, Payette T, Pistone M, Stecker K, Zhang BM, et al: Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci USA. 100:5974–5979. 2003. View Article : Google Scholar : PubMed/NCBI
19	Jung CK, Jung JH, Park GS, Lee A, Kang CS and Lee KY: Expression of transforming acidic coiled-coil containing protein 3 is a novel independent prognostic marker in non-small cell lung cancer. Pathol Int. 56:503–509. 2006. View Article : Google Scholar : PubMed/NCBI
20	Yim EK, Tong SY, Ho EM, Bae JH, Um SJ and Park JS: Anticancer effects on TACC3 by treatment of paclitaxel in HPV-18 positive cervical carcinoma cells. Oncol Rep. 21:549–557. 2009.PubMed/NCBI
21	Ha GH, Kim JL and Breuer EK: TACC3 is essential for EGF-mediated EMT in cervical cancer. PLoS One. 8:e703532013. View Article : Google Scholar : PubMed/NCBI
22	Ha GH, Park JS and Breuer EK: TACC3 promotes epithelial-mesenchymal transition (EMT) through the activation of PI3K/Akt and ERK signaling pathways. Cancer Lett. 332:63–73. 2013. View Article : Google Scholar : PubMed/NCBI
23	Yao R, Natsume Y, Saiki Y, Shioya H, Takeuchi K, Yamori T, Toki H, Aoki I, Saga T and Noda T: Disruption of Tacc3 function leads to in vivo tumor regression. Oncogene. 31:135–148. 2012. View Article : Google Scholar
24	Kiemeney LA, Sulem P, Besenbacher S, Vermeulen SH, Sigurdsson A, Thorleifsson G, Gudbjartsson DF, Stacey SN, Gudmundsson J, Zanon C, et al: A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nat Genet. 42:415–419. 2010. View Article : Google Scholar : PubMed/NCBI
25	Seidl S, Kaufmann H and Drach J: New insights into the pathophysiology of multiple myeloma. Lancet Oncol. 4:557–564. 2003. View Article : Google Scholar : PubMed/NCBI
26	Birrer MJ, Johnson ME, Hao K, Wong KK, Park DC, Bell A, Welch WR, Berkowitz RS and Mok SC: Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas. J Clin Oncol. 25:2281–2287. 2007. View Article : Google Scholar : PubMed/NCBI
27	Singh D, Chan JM, Zoppoli P, Niola F, Sullivan R, Castano A, Liu EM, Reichel J, Porrati P, Pellegatta S, et al: Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 337:1231–1235. 2012. View Article : Google Scholar : PubMed/NCBI
28	Parker BC, Annala MJ, Cogdell DE, Granberg KJ, Sun Y, Ji P, Li X, Gumin J, Zheng H, Hu L, et al: The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J Clin Invest. 123:855–865. 2013.PubMed/NCBI
29	Ha GH, Kim JL, Petersson A, Oh S, Denning MF, Patel T and Breuer EK: TACC3 deregulates the DNA damage response and confers sensitivity to radiation and PARP inhibition. Oncogene. 34:1667–1678. 2015. View Article : Google Scholar
30	Zlobec I, Steele R, Terracciano L, Jass JR and Lugli A: Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 60:1112–1116. 2007. View Article : Google Scholar
31	D'Errico M, De Rinaldis E, Blasi MF, Viti V, Falchetti M, Calcagnile A, Sera F, Saieva C, Ottini L, Palli D, et al: Genome-wide expression profile of sporadic gastric cancers with microsatellite instability. Eur J Cancer. 45:461–469. 2009. View Article : Google Scholar
32	Still IH, Vince P and 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. 58:165–170. 1999. View Article : Google Scholar : PubMed/NCBI
33	Ulisse S, Baldini E, Toller M, Delcros JG, Guého A, Curcio F, De Antoni E, Giacomelli L, Ambesi-Impiombato FS, Bocchini S, et al: Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues. Endocr Relat Cancer. 14:827–837. 2007. View Article : Google Scholar : PubMed/NCBI
34	Lauffart B, Vaughan MM, Eddy R, Chervinsky D, DiCioccio RA, Black JD and Still IH: Aberrations of TACC1 and TACC3 are associated with ovarian cancer. BMC Womens Health. 5:82005. View Article : Google Scholar : PubMed/NCBI
35	Angrisano T, Lembo F, Pero R, Natale F, Fusco A, Avvedimento VE, Bruni CB and Chiariotti L: TACC3 mediates the association of MBD2 with histone acetyltransferases and relieves transcriptional repression of methylated promoters. Nucleic Acids Res. 34:364–372. 2006. View Article : Google Scholar : PubMed/NCBI
36	Sadek CM, Pelto-Huikko M, Tujague M, Steffensen KR, Wennerholm M and Gustafsson JA: TACC3 expression is tightly regulated during early differentiation. Gene Expr Patterns. 3:203–211. 2003. View Article : Google Scholar : PubMed/NCBI
37	Fielding AB, Lim S, Montgomery K, Dobreva I and Dedhar S: A critical role of integrin-linked kinase, ch-TOG and TACC3 in centrosome clustering in cancer cells. Oncogene. 30:521–534. 2011. View Article : Google Scholar
38	Schmidt S, Schneider L, Essmann F, Cirstea IC, Kuck F, Kletke A, Jänicke RU, Wiek C, Hanenberg H, Ahmadian MR, et al: The centrosomal protein TACC3 controls paclitaxel sensitivity by modulating a premature senescence program. Oncogene. 29:6184–6192. 2010. View Article : Google Scholar : PubMed/NCBI
39	Schneider L, Essmann F, Kletke A, Rio P, Hanenberg H, Schulze-Osthoff K, Nürnberg B and Piekorz RP: TACC3 depletion sensitizes to paclitaxel-induced cell death and overrides p21WAF-mediated cell cycle arrest. Oncogene. 27:116–125. 2008. View Article : Google Scholar