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

Cancer Genomics Proteomics. 2018 Mar-Apr;15(2):127-141. doi: 10.21873/cgp.20071.

Abstract

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.

Keywords: EMT; ILK; cancer stem cells; chemoresistance; chemotherapy; colorectal cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Caco-2 Cells
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition
  • Female
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • integrin-linked kinase
  • Protein Serine-Threonine Kinases