In silico analysis of the transportome in human pancreatic ductal adenocarcinoma

被引:16
作者
Zaccagnino, A. [1 ]
Pilarsky, C. [2 ]
Tawfik, D. [1 ]
Sebens, S. [1 ]
Trauzold, A. [1 ]
Novak, I. [3 ]
Schwab, A. [4 ]
Kalthoff, H. [1 ]
机构
[1] Univ Kiel, UKSH, Inst Expt Canc Res, Campus Kiel,Arnold Heller Str 3, D-24105 Kiel, Germany
[2] Univ Clin, Dept Surg, Krankenhausstr 12, D-91054 Erlangen, Germany
[3] Univ Copenhagen, Fac Sci, Dept Biol, Sect Cell Biol & Physiol, Univ Pk 13, DK-2100 Copenhagen, Denmark
[4] Univ Munster, Inst Physiol 2, Robert Koch Str 27 b, D-48149 Munster, Germany
来源
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS | 2016年 / 45卷 / 07期
关键词
Pancreatic ductal adenocarcinoma; Tumor stroma; Chronic pancreatitis; Gene expression analysis; Ion channels; Transportome; EPITHELIAL-MESENCHYMAL TRANSITION; CA2+-ACTIVATED K+ CHANNELS; HUMAN PROSTATE-CANCER; ACID-BASE TRANSPORT; POTASSIUM CHANNELS; GENE-EXPRESSION; ION CHANNELS; CELL-ADHESION; GROWTH; RECEPTORS;
D O I
10.1007/s00249-016-1171-9
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
The altered expression and/or activity of ion channels and transporters (transportome) have been associated with malignant behavior of cancer cells and were proposed to be a hallmark of cancer. However, the impact of altered transportome in epithelial cancers, such as pancreatic ductal adenocarcinoma (PDAC), as well as its pathophysiological consequences, still remains unclear. Here, we report the in silico analysis of 840 transportome genes in PDAC patients' tissues. Our study was focused on the transportome changes and their correlation with functional and behavioral responses in PDAC tumor and stromal compartments. The dysregulated gene expression datasets were filtered using a cut-off of fold-change values <=-2 or >= 2 (adjusted p value <= 0.05). The dysregulated transportome genes were clearly associated with impaired physiological secretory mechanisms and/or pH regulation, control of cell volume, and cell polarity. Additionally, some down-regulated transportome genes were found to be closely linked to epithelial cell differentiation. Furthermore, the observed decrease in genes coding for calcium and chloride transport might be a mechanism for evasion of apoptosis. In conclusion, the current work provides a comprehensive overview of the altered transportome expression and its association with predicted PDAC malignancy with special focus on the epithelial compartment.
引用
收藏
页码:749 / 763
页数:15
相关论文
共 91 条
[31]   Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays [J].
Grützmann, R ;
Pilarsky, C ;
Ammerpohl, O ;
Lüttges, J ;
Böhme, A ;
Sipos, B ;
Foerder, M ;
Alldinger, I ;
Jahnke, B ;
Schackert, HK ;
Kalthoff, H ;
Kremer, B ;
Klöppel, G ;
Saeger, HD .
NEOPLASIA, 2004, 6 (05) :611-622
[32]   The P2X7 Receptor Supports Both Life and Death in Fibrogenic Pancreatic Stellate Cells [J].
Haanes, Kristian A. ;
Schwab, Albrecht ;
Novak, Ivana .
PLOS ONE, 2012, 7 (12)
[33]   The hallmarks of cancer [J].
Hanahan, D ;
Weinberg, RA .
CELL, 2000, 100 (01) :57-70
[34]   Hallmarks of Cancer: The Next Generation [J].
Hanahan, Douglas ;
Weinberg, Robert A. .
CELL, 2011, 144 (05) :646-674
[35]   The Reactome BioMart [J].
Haw, Robin A. ;
Croft, David ;
Yung, Christina K. ;
Ndegwa, Nelson ;
D'Eustachio, Peter ;
Hermjakob, Henning ;
Stein, Lincoln D. .
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION, 2011,
[36]   Molecular basis of potassium channels in pancreatic duct epithelial cells [J].
Hayashi, Mikio ;
Novak, Ivana .
CHANNELS, 2013, 7 (06) :432-441
[37]  
Holzer Peter, 2009, Handb Exp Pharmacol, P283, DOI 10.1007/978-3-540-79090-7_9
[38]   Epithelial to mesenchymal transition: Expression of the regulators snail, slug, and twist in pancreatic cancer [J].
Hotz, Birgit ;
Arndt, Marco ;
Dullat, Sonja ;
Bhargava, Sarah ;
Buhr, Heinz-J. ;
Hotz, Hubert G. .
CLINICAL CANCER RESEARCH, 2007, 13 (16) :4769-4776
[39]   Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model [J].
Hu, Jinwei ;
Yuan, Xiangpeng ;
Ko, MinHee K. ;
Yin, Dali ;
Sacapano, Manuel R. ;
Wang, Xiao ;
Konda, Bindu M. ;
Espinoza, Andres ;
Prosolovich, Ksenia ;
Ong, John M. ;
Irvin, Dwain ;
Black, Keith L. .
MOLECULAR CANCER, 2007, 6
[40]   Targeting potassium channels in cancer [J].
Huang, Xi ;
Jan, Lily Yeh .
JOURNAL OF CELL BIOLOGY, 2014, 206 (02) :151-162