ILK Expression in Colorectal Cancer Is Associated with EMT, Cancer Stem Cell Markers and Chemoresistance

被引：70
作者：
Tsoumas, Dimitrios [1 ]
Nikou, Sofia [1 ]
Giannopoulou, Efstathia [2 ]
Tsaniras, Spyridon Champeris [3 ]
Sirinian, Chaido [2 ]
Maroulis, Ioannis [4 ]
Taraviras, Stavros [3 ]
Zolota, Vassiliki [5 ]
Kalofonos, Haralabos P. [2 ]
Bravou, Vasiliki [1 ]
机构：
[1] Univ Patras, Med Sch, Dept Anat Histol Embryol, Patras 26500, Greece
[2] Univ Patras, Clin Oncol Lab, Med Sch, Patras, Greece
[3] Univ Patras, Med Sch, Dept Physiol, Patras, Greece
[4] Univ Patras, Med Sch, Dept Surg, Patras, Greece
[5] Univ Patras, Med Sch, Dept Pathol, Patras, Greece
来源：
CANCER GENOMICS & PROTEOMICS | 2018年 / 15卷 / 02期
关键词：
ILK; EMT; chemotherapy; chemoresistance; colorectal cancer; cancer stem cells; INTEGRIN-LINKED KINASE; EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN COLON-CANCER; BETA-CATENIN; E-CADHERIN; TUMOR PROGRESSION; DRUG-RESISTANCE; CARCINOMA CELLS; OVEREXPRESSION; SNAIL;
D O I：
10.21873/cgp.20071
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background/Aim: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers. Patients and Methods: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples. We also generated colon cancer cells resistant to 5-FU and oxaliplatin and studied the effect of ILK inhibition on drug response by MTT assay and on EMT and CSC markers' expression. Results: ILK expression in human CRC correlates with EMT and CSC markers and is associated with metastasis and chemoresistance. ILK inhibition increases sensitivity of resistant cells to 5-FU and oxaliplatin and reduces the levels of EMT and CSC markers in 5-FU resistant cells. Conclusion: ILK overexpression in human CRC associates with EMT and CSC traits, contributing to tumor progression and chemoresistance.
引用
收藏
页码：127 / 141
页数：15
相关论文
共 63 条
[1]  
Amin M.B., 2017, AM JOINT COMMITTEE C, V8th
[2]   Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].
Barker, Nick ;
van Es, Johan H. ;
Kuipers, Jeroen ;
Kujala, Pekka ;
van den Born, Maaike ;
Cozijnsen, Miranda ;
Haegebarth, Andrea ;
Korving, Jeroen ;
Begthel, Harry ;
Peters, Peter J. ;
Clevers, Hans .
NATURE, 2007, 449 (7165) :1003-U1
[3]  
Batsaikhan BE, 2014, ANTICANCER RES, V34, P6339
[4]  
Bosman FT, 2010, WHO Classification of tumors of the digestive system, V4th
[5]   Invasion and metastasis in colorectal cancer:: Epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and β-catenin [J].
Brabletz, T ;
Hlubek, F ;
Spaderna, S ;
Schmalhofer, O ;
Hiendlmeyer, E ;
Jung, A ;
Kirchner, T .
CELLS TISSUES ORGANS, 2005, 179 (1-2) :56-65
[6]   ILK over-expression in human colon cancer progression correlates with activation of β-catenin, down-regulation of E-cadherin and activation of the Akt-FKHR pathway [J].
Bravou, V ;
Klironomos, G ;
Papadaki, E ;
Taraviras, S ;
Varakis, J .
JOURNAL OF PATHOLOGY, 2006, 208 (01) :91-99
[7]   Integrin-linked kinase (ILK) expression in human colon cancer [J].
Bravou, V ;
Klironomos, G ;
Papadaki, E ;
Stefanou, D ;
Varakis, J .
BRITISH JOURNAL OF CANCER, 2003, 89 (12) :2340-2341
[8]   The cancer stem cell: premises, promises and challenges [J].
Clevers, Hans .
NATURE MEDICINE, 2011, 17 (03) :313-319
[9]  
Coley HM, 2004, METH MOLEC MED, V88, P267
[10]   Phenotypic characterization of human colorectal cancer stem cells [J].
Dalerba, Piero ;
Dylla, Scott J. ;
Park, In-Kyung ;
Liu, Rui ;
Wang, Xinhao ;
Cho, Robert W. ;
Hoey, Timothy ;
Gurney, Austin ;
Huang, Emina H. ;
Simeone, Diane M. ;
Shelton, Andrew A. ;
Parmiani, Giorgio ;
Castelli, Chiara ;
Clarke, Michael F. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (24) :10158-10163
1234567