Skip to main content
Erschienen in: Tumor Biology 1/2016

14.08.2015 | Original Article

TNIK serves as a novel biomarker associated with poor prognosis in patients with pancreatic cancer

verfasst von: Yong Zhang, Hongwei Jiang, Mingfang Qin, Xiangyu Su, Zhanguo Cao, Ju Wang

Erschienen in: Tumor Biology | Ausgabe 1/2016

Einloggen, um Zugang zu erhalten

Abstract

Traf-2 and Nck interacting kinase (TNIK) is one of the STE20/MAP4K family members implicated in carcinogenesis and progression of several human malignancies. However, its expression pattern and biological behavior in pancreatic carcinoma remains completely unclear. The present study is designed to investigate the clinical and prognostic value of TNIK in pancreatic carcinoma. TNIK mRNA and protein level was respectively detected by real-time quantitative RCR (qPCR) and Western blot in ten paired samples of pancreatic cancer. Immunohistochemical staining was also conducted to examine TNIK in the tissue microarray (TMA) consisting of 91 archived specimens of pancreatic cancer. The correlation between TNIK and prognosis was assessed by Kaplan–Meier curves and Cox regression. The mRNA and protein levels of TNIK in pancreatic cancer were both significantly higher than those in matched paratumor tissues. Immunohistochemistry analysis showed that TNIK was positively associated with pathologic T (P = 0.045) and TNM (P = 0.040) stage. In addition, The Kaplan–Meier survival curves indicated that patients with high expression of TNIK had a shorter overall survival (OS) and disease-free survival (DFS) than those with low expression. Our results demonstrated that TNIK might play a crucial role in pancreatic carcinogenesis and serve as a novel therapeutic target of pancreatic cancer.
Literatur
1.
4.
Zurück zum Zitat Fu CA, Shen M, Huang BC, Lasaga J, Payan DG, Luo Y. TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton. J Biol Chem. 1999;274:30729–37.CrossRefPubMed Fu CA, Shen M, Huang BC, Lasaga J, Payan DG, Luo Y. TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton. J Biol Chem. 1999;274:30729–37.CrossRefPubMed
5.
Zurück zum Zitat Taira K, Umikawa M, Takei K, Myagmar BE, Shinzato M, Machida N, et al. The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. J Biol Chem. 2004;279:49488–96.CrossRefPubMed Taira K, Umikawa M, Takei K, Myagmar BE, Shinzato M, Machida N, et al. The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. J Biol Chem. 2004;279:49488–96.CrossRefPubMed
6.
Zurück zum Zitat Mahmoudi T, Li VS, Ng SS, Taouatas N, Vries RG, Mohammed S, et al. The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 2009;28:3329–40.CrossRefPubMedPubMedCentral Mahmoudi T, Li VS, Ng SS, Taouatas N, Vries RG, Mohammed S, et al. The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 2009;28:3329–40.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Shitashige M, Satow R, Jigami T, Aoki K, Honda K, Shibata T, et al. Traf2- and Nck-interacting kinase is essential for Wnt signaling and colorectal cancer growth. Cancer Res. 2010;70:5024–33.CrossRefPubMed Shitashige M, Satow R, Jigami T, Aoki K, Honda K, Shibata T, et al. Traf2- and Nck-interacting kinase is essential for Wnt signaling and colorectal cancer growth. Cancer Res. 2010;70:5024–33.CrossRefPubMed
8.
Zurück zum Zitat Yu DH, Zhang X, Wang H, Zhang L, Chen H, Hu M, et al. The essential role of TNIK gene amplification in gastric cancer growth. Oncogenesis. 2014;3, e93.CrossRefPubMedPubMedCentral Yu DH, Zhang X, Wang H, Zhang L, Chen H, Hu M, et al. The essential role of TNIK gene amplification in gastric cancer growth. Oncogenesis. 2014;3, e93.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Wang H, Zhang W, Fuller GN. Tissue microarrays: applications in neuropathology research, diagnosis, and education. Brain Pathol. 2002;12:95–107.CrossRefPubMed Wang H, Zhang W, Fuller GN. Tissue microarrays: applications in neuropathology research, diagnosis, and education. Brain Pathol. 2002;12:95–107.CrossRefPubMed
10.
Zurück zum Zitat Hussain NK, Hsin H, Huganir RL, Sheng M. MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function. J Neurosci. 2010;30:14786–94.CrossRefPubMedPubMedCentral Hussain NK, Hsin H, Huganir RL, Sheng M. MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function. J Neurosci. 2010;30:14786–94.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Kawabe H, Neeb A, Dimova K, Young Jr SM, Takeda M, Katsurabayashi S, et al. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010;65:358–72.CrossRefPubMedPubMedCentral Kawabe H, Neeb A, Dimova K, Young Jr SM, Takeda M, Katsurabayashi S, et al. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010;65:358–72.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Satow R, Shitashige M, Jigami T, Honda K, Ono M, Hirohashi S, et al. Traf2- and Nck-interacting kinase is essential for canonical Wnt signaling in Xenopus axis formation. J Biol Chem. 2010;285:26289–94.CrossRefPubMedPubMedCentral Satow R, Shitashige M, Jigami T, Honda K, Ono M, Hirohashi S, et al. Traf2- and Nck-interacting kinase is essential for canonical Wnt signaling in Xenopus axis formation. J Biol Chem. 2010;285:26289–94.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Ju B, Spitsbergen J, Eden CJ, Taylor MR, Chen W. Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish. Mol Cancer. 2009;8:40.CrossRefPubMedPubMedCentral Ju B, Spitsbergen J, Eden CJ, Taylor MR, Chen W. Co-activation of hedgehog and AKT pathways promote tumorigenesis in zebrafish. Mol Cancer. 2009;8:40.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Boyer A, Goff AK, Boerboom D. Wnt signaling in ovarian follicle biology and tumorigenesis. Trends Endocrinol Metab. 2010;21:25–32.CrossRefPubMed Boyer A, Goff AK, Boerboom D. Wnt signaling in ovarian follicle biology and tumorigenesis. Trends Endocrinol Metab. 2010;21:25–32.CrossRefPubMed
15.
Zurück zum Zitat Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Cell Biol. 2007;19:142–9.CrossRefPubMed Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Cell Biol. 2007;19:142–9.CrossRefPubMed
16.
17.
Zurück zum Zitat Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.CrossRefPubMed Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.CrossRefPubMed
18.
Zurück zum Zitat Shkoda A, Town JA, Griese J, Romio M, Sarioglu H, Knofel T, et al. The germinal center kinase TNIK is required for canonical NF-kappaB and JNK signaling in B-cells by the EBV oncoprotein LMP1 and the CD40 receptor. PLoS Biol. 2012;10, e1001376.CrossRefPubMedPubMedCentral Shkoda A, Town JA, Griese J, Romio M, Sarioglu H, Knofel T, et al. The germinal center kinase TNIK is required for canonical NF-kappaB and JNK signaling in B-cells by the EBV oncoprotein LMP1 and the CD40 receptor. PLoS Biol. 2012;10, e1001376.CrossRefPubMedPubMedCentral
Metadaten
Titel
TNIK serves as a novel biomarker associated with poor prognosis in patients with pancreatic cancer
verfasst von
Yong Zhang
Hongwei Jiang
Mingfang Qin
Xiangyu Su
Zhanguo Cao
Ju Wang
Publikationsdatum
14.08.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 1/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3881-5

Weitere Artikel der Ausgabe 1/2016

Tumor Biology 1/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.