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

doi:10.1158/1541-7786.MCR-21-0388

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

Urology

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English (US)
Pages (from-to)	527-541
Number of pages	15
Journal	Molecular Cancer Research
Volume	20
Issue number	4
DOIs	https://doi.org/10.1158/1541-7786.MCR-21-0388
State	Published - Apr 2022

ASJC Scopus subject areas

Molecular Biology
Oncology
Cancer Research

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10.1158/1541-7786.MCR-21-0388

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Van den Broeck, T., Moris, L., Gevaert, T., Davicioni, E., Boeckx, B., Lambrechts, D., Helsen, C., Handle, F., Ghesquiere, B., Soenen, S., Smeets, E., Eerlings, R., El Kharraz, S., Devlies, W., Karnes, R. J., Lotan, T., Van Poppel, H., Joniau, S., & Claessens, F. (2022). Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer. Molecular Cancer Research, 20(4), 527-541. https://doi.org/10.1158/1541-7786.MCR-21-0388

Van den Broeck, T, Moris, L, Gevaert, T, Davicioni, E, Boeckx, B, Lambrechts, D, Helsen, C, Handle, F, Ghesquiere, B, Soenen, S, Smeets, E, Eerlings, R, El Kharraz, S, Devlies, W, Karnes, RJ, Lotan, T, Van Poppel, H, Joniau, S & Claessens, F 2022, 'Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer', Molecular Cancer Research, vol. 20, no. 4, pp. 527-541. https://doi.org/10.1158/1541-7786.MCR-21-0388

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

abstract = "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.",

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

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doi = "10.1158/1541-7786.MCR-21-0388",

language = "English (US)",

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T1 - Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer

AU - Van den Broeck, Thomas

AU - Moris, Lisa

AU - Gevaert, Thomas

AU - Davicioni, Elai

AU - Boeckx, Bram

AU - Lambrechts, Diether

AU - Helsen, Christine

AU - Handle, Florian

AU - Ghesquiere, Bart

AU - Soenen, Stefaan

AU - Smeets, Elien

AU - Eerlings, Roy

AU - El Kharraz, Sarah

AU - Devlies, Wout

AU - Karnes, R. Jeffrey

AU - Lotan, Tamara

AU - Van Poppel, Hendrik

AU - Joniau, Steven

AU - Claessens, Frank

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

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

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