α‑taxilin overexpression correlates with proliferation activity but not with prognosis of colorectal cancer

Kanamori,Akira; Imai,Yasuo; Ihara,Keisuke; Nagata,Hitoshi; Nakano,Masakazu; Tominaga,Keiichi; Shimizu,Hiroaki; Makiyama,Tomihiko; Kuroda,Hajime; Shirataki,Hiromichi; Hiraishi,Hideyuki

doi:10.3892/ol.2017.6309

α‑taxilin overexpression correlates with proliferation activity but not with prognosis of colorectal cancer

Authors:
- Akira Kanamori
- Yasuo Imai
- Keisuke Ihara
- Hitoshi Nagata
- Masakazu Nakano
- Keiichi Tominaga
- Hiroaki Shimizu
- Tomihiko Makiyama
- Hajime Kuroda
- Hiromichi Shirataki
- Hideyuki Hiraishi
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Affiliations: Department of Gastroenterology, School of Medicine, Dokkyo Medical University, Mibu, Tochigi 321‑0293, Japan, Department of Diagnostic Pathology, School of Medicine, Dokkyo Medical University, Mibu, Tochigi 321‑0293, Japan, Department of Surgical Oncology, School of Medicine, Dokkyo Medical University, Mibu, Tochigi 321‑0293, Japan, Department of Gastroenterological Surgery, School of Medicine, Dokkyo Medical University, Mibu, Tochigi 321‑0293, Japan, Department of Molecular and Cell Biology, School of Medicine, Dokkyo Medical University, Mibu, Tochigi 321‑0293, Japan
Published online on: June 2, 2017 https://doi.org/10.3892/ol.2017.6309
Pages: 1471-1476
Copyright: © Kanamori et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

α‑taxilin is a binding partner of syntaxins, which are the central coordinators of membrane traffic. Expression of α‑taxilin has been implicated in the development of human glioblastoma, hepatocellular carcinoma and renal cell carcinoma. In the present study, the clinical significance of α‑taxilin expression in colorectal cancer (CRC) was investigated. A total of 20 cases of colorectal intramucosal adenocarcinoma (IMA) with adenoma were analyzed using immunohistochemical analysis. The results demonstrated that α‑taxilin expression was significantly associated with Ki‑67 indices in adenoma and IMA. The patients expressed equally high levels of α‑taxilin in the upper third of the intramucosal glands. These results suggest that α‑taxilin expression is significantly associated with the proliferative activity of CRC, but that its overexpression alone is not a biomarker of malignancy. Next, α‑taxilin expression was investigated in 57 advanced CRCs and its association with prognosis was determined. Well‑differentiated and/or moderately differentiated adenocarcinomas in the left‑sided colon with anatomic stage II and/or III were analyzed. α‑taxilin expression levels were high on the surface of nearly all tumors, but variable at the deep advancing edge. α‑taxilin levels at the advancing edge were not significantly associated with local invasiveness or prognosis. In conclusion, α‑taxilin is a cell proliferation marker in colorectal epithelial neoplasms but cannot be a marker of malignancy or prognosis of CRCs.

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1	World Cancer Research Fund/American Institute for Cancer Research, . Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective. AICR; Washington DC: pp. 280–288. 2007
2	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
3	Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr and Kinzler KW: Cancer genome landscapes. Science. 339:1546–1558. 2013. View Article : Google Scholar : PubMed/NCBI
4	Strömberg S, Agnarsdóttir M, Magnusson K, Rexhepaj E, Bolander A, Lundberg E, Asplund A, Ryan D, Rafferty M, Gallagher WM, et al: Selective expression of Syntaxin-7 protein in benign melanocytes and malignant melanoma. J Proteome Res. 8:1639–1646. 2009. View Article : Google Scholar : PubMed/NCBI
5	Hashimoto S, Onodera Y, Hashimoto A, Tanaka M, Hamaguchi M, Yamada A and Sabe H: Requirement for Arf6 in breast cancer invasive activities. Proc Natl Acad Sci USA. 101:pp. 6647–6652. 2004; View Article : Google Scholar : PubMed/NCBI
6	Bascom JL, Fata JE, Hirai Y, Sternlicht MD and Bissell MJ: Epimorphin overexpression in the mouse mammary gland promotes alveolar hyperplasia and mammary adenocarcinoma. Cancer Res. 65:8617–8621. 2005. View Article : Google Scholar : PubMed/NCBI
7	Chen YA and Scheller RH: SNARE-mediated membrane fusion. Nat Rev Mol Cell Biol. 2:98–106. 2001. View Article : Google Scholar : PubMed/NCBI
8	Nogami S, Satoh S, Nakano M, Shimizu H, Fukushima H, Maruyama A, Terano A and Shirataki H: Taxilin; a novel syntaxin-binding protein that is involved in Ca2+-dependent exocytosis in neuroendocrine cells. Genes Cells. 8:17–28. 2003. View Article : Google Scholar : PubMed/NCBI
9	Nogami S, Satoh S, Nakano M, Terano A and Shirataki H: Interaction of taxilin with syntaxin which does not form the SNARE complex. Biochem Biophys Res Commun. 311:797–802. 2003. View Article : Google Scholar : PubMed/NCBI
10	Horii Y, Sakane H, Nogami S, Ohtomo N, Tomiya T and Shirataki H: Expression of α-taxilin in the murine gastrointestinal tract: Potential implication in cell proliferation. Histochem Cell Biol. 141:165–180. 2014. View Article : Google Scholar : PubMed/NCBI
11	Sai XB, Makiyama T, Sakane H, Horii Y, Hiraishi H and Shirataki H: TSG101, a tumor susceptibility gene, bidirectionally modulates cell invasion through regulating MMP-9 mRNA expression. BMC Cancer. 15:9332015. View Article : Google Scholar : PubMed/NCBI
12	Oba-Shinjo SM, Bengtson MH, Winnischofer SM, Colin C, Vedoy CG, De Mendonça Z, Marie SK and Sogayar MC: Identification of novel differentially expressed genes in human astrocytomas by cDNA representational difference analysis. Brain Res Mol Brain Res. 140:25–33. 2005. View Article : Google Scholar : PubMed/NCBI
13	Ohtomo N, Tomiya T, Tanoue Y, Inoue Y, Nishikawa T, Ikeda H, Seyama Y, Kokudo N, Shibahara J, Fukayama M, et al: Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor. Int J Oncol. 37:1417–1423. 2010.PubMed/NCBI
14	Mashidori T, Shirataki H, Kamai T, Nakamura F and Yoshida K: Increased alpha-taxilin protein expression is associated with the metastatic and invasive potential of renal cell cancer. Biomed Res. 32:103–110. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hamilton SR, Bosman FT, Boffetta P, Ilyas M, Morreau H, Nakamura SI, Quirke P, Riboli E and Sobin LH: Carcinoma of the colon and rectumWHO Classification of Tumours of the Digestive System. 4th. Bozman FT, Carneiro F, Hruban RH and Theise ND: IARC Press; Lyon: pp. 134–146. 2010
16	American Joint Committee on Cancer (AJCC), . Colon and Rectum Cancer Staging. 7th. AJCC; Chicago, IL: 2009, https://cancerstaging.org/references-tools/quickreferences/Documents/ColonMedium.pdfMay 25–2017
17	Imai Y: Poorly differentiated adenocarcinoma of the colon: Subsite location and clinicopathologic features. Int J Colorectal Dis. 30:187–196. 2015. View Article : Google Scholar : PubMed/NCBI
18	Sakakibara S, Nakadate K, Tanaka-Nakadate S, Yoshida K, Nogami S, Shirataki H and Ueda S: Developmental and spatial expression pattern of alpha-taxilin in the rat central nervous system. J Comp Neurol. 511:65–80. 2008. View Article : Google Scholar : PubMed/NCBI
19	Fodde R, Smits R and Clevers H: APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer. 1:55–67. 2001. View Article : Google Scholar : PubMed/NCBI
20	Roeb E, Dietrich CG, Winograd R, Arndt M, Breuer B, Fass J, Schumpelick V and Matern S: Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma differential activity of matrix metalloproteinase-9. Cancer. 92:2680–2691. 2001. View Article : Google Scholar : PubMed/NCBI
21	Behrens P, Mathiak M, Mangold E, Kirdorf S, Wellmann A, Fogt F, Rothe M, Florin A and Wernert N: Stromal expression of invasion-promoting, matrix-degrading proteases MMP-1 and −9 and the Ets 1 transcription factor in HNPCC carcinomas and sporadic colorectal cancers. Int J Cancer. 107:183–188. 2003. View Article : Google Scholar : PubMed/NCBI
22	Said AH, Raufman JP and Xie G: The role of matrix metalloproteinases in colorectal cancer. Cancers (Basel). 6:366–375. 2014. View Article : Google Scholar : PubMed/NCBI
23	Zeng ZS, Huang Y, Cohen AM and Guillem JG: Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol. 14:3133–3140. 1996. View Article : Google Scholar : PubMed/NCBI
24	Zeng ZS, Cohen AM and Guillem JG: Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis. Carcinogenesis. 20:749–755. 1999. View Article : Google Scholar : PubMed/NCBI
25	Kean MJ, Williams KC, Skalski M, Myers D, Burtnik A, Foster D and Coppolino MG: VAMP3, syntaxin-13 and SNAP23 are involved in secretion of matrix metalloproteinases, degradation of the extracellular matrix and cell invasion. J Cell Sci. 122:4089–4098. 2009. View Article : Google Scholar : PubMed/NCBI