Integrin-Linked-Kinase Overexpression Is Implicated in Mechanisms of Genomic Instability in Human Colorectal Cancer.

Abstract

BACKGROUND:

Genomic instability is a hallmark of cancer cells contributing to tumor development and progression. Integrin-linked kinase (ILK) is a focal adhesion protein with well-established role in carcinogenesis. We have previously shown that ILK overexpression is critically implicated in human colorectal cancer (CRC) progression. In light of the recent findings that ILK regulates centrosomes and mitotic spindle formation, we aimed to determine its implication in mechanisms of genomic instability in human CRC.

METHODS:

Association of ILK expression with markers of genomic instability (micronuclei formation, nucleus size, and intensity) was investigated in diploid human colon cancer cells HCT116 upon ectopic ILK overexpression, by immunofluorescence and in human CRC samples by Feulgen staining. We also evaluated the role of ILK in mitotic spindle formation, by immunofluorescence, in HCT116 cells upon inhibition and overexpression of ILK. Finally, we evaluated association of ILK overexpression with markers of DNA damage (p-H2AX, p-ATM/ATR) in human CRC tissue samples by immunohistochemistry and in ILK-overexpressing cells by immunofluorescence.

RESULTS:

We showed that ILK overexpression is associated with genomic instability markers in human colon cancer cells and tissues samples. Aberrant mitotic spindles were observed in cells treated with specific ILK inhibitor (QLT0267), while ILK-overexpressing cells failed to undergo nocodazole-induced mitotic arrest. ILK overexpression was also associated with markers of DNA damage in HCT116 cells and human CRC tissue samples.

CONCLUSIONS:

The above findings indicate that overexpression of ILK is implicated in mechanisms of genomic instability in CRC suggesting a novel role of this protein in cancer.

• Authors: Panagiota Chadla, Marina Arbi, Sofia Nikou, Theodoros Kalliakoudas, Helen Papadaki, Stavros Taraviras, Zoi Lygerou, Vasiliki Bravou
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 66 Issue 5 Pg. 1510-1523 (05 2021) ISSN: 1573-2568 [Electronic] United States
• PMID: 32495257 (Publication Type: Journal Article)

Chemical References

• H2AX protein, human
• Histones
• integrin-linked kinase
• ATM protein, human
• ATR protein, human
• Ataxia Telangiectasia Mutated Proteins
• Protein Serine-Threonine Kinases

Topics

• Ataxia Telangiectasia Mutated Proteins (metabolism)
• Colorectal Neoplasms (enzymology, genetics, pathology)
• DNA Damage
• Genomic Instability
• HCT116 Cells
• Histones (metabolism)
• Humans
• Micronuclei, Chromosome-Defective
• Phosphorylation
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Signal Transduction
• Spindle Apparatus (enzymology, genetics, pathology)