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

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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.

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Acknowledgments

We thank the Advanced Light Microscopy Unit of the Medical School at the University of Patras. We are also grateful to Dr. Alexandra Kanellou and Dr. Andreas Panagopoulos for their assistance and helpful discussions.

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Authors and Affiliations

  1. Department of Anatomy, Histology and Embryology, Medical School, University of Patras, Rio, 26500, Greece

    Panagiota Chadla, Sofia Nikou, Helen Papadaki & Vasiliki Bravou

  2. Department of Biology, Medical School, University of Patras, Rio, Greece

    Marina Arbi & Zoi Lygerou

  3. Department of Physiology, Medical School, University of Patras, Rio, Greece

    Theodoros Kalliakoudas & Stavros Taraviras

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  1. Panagiota Chadla
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  2. Marina Arbi
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  3. Sofia Nikou
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  4. Theodoros Kalliakoudas
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  8. Vasiliki Bravou
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Correspondence to Vasiliki Bravou.

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Ethical approval

The study was performed in accordance with the Helsinki Declaration and was approved by the Committee on Research and Ethics and the Scientific Committee of the University Hospital of Patras, Greece. Since archival tissue blocks were used retrospectively, a written informed consent was waived by the ethics committee.

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Chadla, P., Arbi, M., Nikou, S. et al. Integrin-Linked-Kinase Overexpression Is Implicated in Mechanisms of Genomic Instability in Human Colorectal Cancer. Dig Dis Sci 66, 1510–1523 (2021). https://doi.org/10.1007/s10620-020-06364-6

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  • DOI: https://doi.org/10.1007/s10620-020-06364-6

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