title: Phosphoglycerate kinase 1 as a promoter of metastasis in colon cancer.
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.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Sufian S
authors.initials: SS
authors.lastname: Ahmad
authors.forename: Jörg
authors.initials: J
authors.lastname: Glatzle
authors.forename: Khaled
authors.initials: K
authors.lastname: Bajaeifer
authors.forename: Sarah
authors.initials: S
authors.lastname: Bühler
authors.forename: Thorsten
authors.initials: T
authors.lastname: Lehmann
authors.forename: Ingmar
authors.initials: I
authors.lastname: Königsrainer
authors.forename: Jörg-Peter
authors.initials: JP
authors.lastname: Vollmer
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Suhaib S
authors.initials: SS
authors.lastname: Ahmad
authors.forename: Hinnak
authors.initials: H
authors.lastname: Northoff
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.forename: Derek
authors.initials: D
authors.lastname: Zieker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D055515:Cysteine-Rich Protein 61 / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018384:Oxidative Stress; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; C577282:PGK1 protein, human; D010735:Phosphoglycerate Kinase