Phosphoglycerate kinase 1 as a promoter of metastasis in colon cancer

Ahmad,Sufian   S.; Glatzle,Jörg; Bajaeifer,Khaled; Bühler,Sarah; Lehmann,Thorsten; Königsrainer,Ingmar; Vollmer,Jörg-Peter; Sipos,Bence; Ahmad,Suhaib  S.; Northoff,Hinnak; Königsrainer,Alfred; Zieker,Derek

doi:10.3892/ijo.2013.1971

Phosphoglycerate kinase 1 as a promoter of metastasis in colon cancer

Authors:
- Sufian S. Ahmad
- Jörg Glatzle
- Khaled Bajaeifer
- Sarah Bühler
- Thorsten Lehmann
- Ingmar Königsrainer
- Jörg-Peter Vollmer
- Bence Sipos
- Suhaib S. Ahmad
- Hinnak Northoff
- Alfred Königsrainer
- Derek Zieker
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Affiliations: Department of General, Visceral and Transplantation Surgery, University of Tübingen, D-72076 Tübingen, Germany, Institute for Clinical and Experimental Transfusion Medicine, University of Tübingen, D-72076 Tübingen, Germany, Institute of Pathology and Neuropathology, University of Tübingen, D-72076 Tübingen, Germany
Published online on: May 31, 2013 https://doi.org/10.3892/ijo.2013.1971
Pages: 586-590

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Abstract

Oxidative stress due to intratumoral hypoxia in solid cancer has been shown to be associated with increased mortality. Phosphoglycerate kinase 1 (PGK1) is an enzyme of the glycolytic pathway, which is regulated by hypoxia-inducible factor-1α (HIF-1α) and has been described for its role in tumor progression and metastasis in several malignancies. We investigated whether the expression of PGK1 varies between metastatic and non-metastatic colon cancer. We compared PGK1 expression in colon cancer patients either with or without metastasis via polymerase chain reaction (PCR) and immunohistochemistry. Microarray analysis was performed to test altered gene expression after PGK1 silencing, using isolates from HCT116 cell lines. PCR results showed an increased expression of PGK1 in colon cancer tissue from metastatic patients in comparison to patients with no metastasis (fold change 2.6, p<0.001). Immunohistochemical staining of PGK1 showed stronger staining in metastatic tissue in comparison to non-metastatic cancer tissue according to a semi-quantitative evaluation. Microarray and subsequent pathway analysis provided 4 genes of interest (CYR61, FOS, JUN and EGR1) used for pathway proposal. The results indicate that increased expression of PGK1 in colon cancer tissue is associated with metastasis. Furthermore, we propose several genes induced by PGK1 that could account for cell migration, mainly EGR1 and CYR61 together with the transcription factors FOS and JUN.

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