Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer

Thomas Van den Broeck, Lisa Moris, Thomas Gevaert, Elai Davicioni, Bram Boeckx, Diether Lambrechts, Christine Helsen, Florian Handle, Bart Ghesquiere, Stefaan Soenen, Elien Smeets, Roy Eerlings, Sarah El Kharraz, Wout Devlies, R. Jeffrey Karnes, Tamara Lotan, Hendrik Van Poppel, Steven Joniau, Frank Claessens

Research output: Contribution to journalArticlepeer-review


Molecular drivers of metastasis in patients with high-risk local-pendent cohorts. The effects of AZIN1 knockdown were evaluated, ized prostate cancer are poorly understood. Therefore, we aim to due to its therapeutic potential. AZIN1 knockdown effected pro-study molecular drivers of metastatic progression in patients with liferation and metastatic potential of prostate cancer cells and high-risk prostate cancer. A retrospective matched case-control xenograft models. RNA sequencing after AZIN1 knockdown in study of two clinico-pathologically identical groups of patients with prostate cancer cells revealed upregulation of genes coding for high-risk prostate cancer was undertaken. One group developed collagen subunits. The observed effect on cell migration after AZIN1 metastatic recurrence (n = 19) while the other did not (n = 25). The knockdown was mimicked when exposing prostate cancer cells to primary index tumor was identified by a uro-pathologist, followed bio-active molecules deriving from COL4A1 and COL4A2. Our by DNA and RNA extraction for somatic copy-number aberration integrated CNA and gene expression analysis of primary high-risk (SCNA) analysis and whole-transcriptome gene expression analyprostate cancer identified the AZIN1 gene as a novel driver of sis. In vitro and in vivo studies included cell line manipulation and metastatic progression, by altering collagen subunit expression.xenograft models. Future research should further investigate its therapeutic potential The integrative CNA and gene expression analyses identified an in preventing metastatic recurrence. increase in Antizyme Inhibitor 1 (AZIN1) gene expression within a focal amplification of 8q22.3, which was associated with metastatic Implications: AZIN1 was identified as driver of metastatic pro-recurrence of patients with high-risk prostate cancer in four indegression in high-risk prostate cancer through matrikine regulation.

Original languageEnglish (US)
Pages (from-to)527-541
Number of pages15
JournalMolecular Cancer Research
Issue number4
StatePublished - Apr 2022

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research


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