FRMD6 has tumor suppressor functions in prostate cancer

Research output: Contribution to journal › Journal article › Research › peer-review

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FRMD6 has tumor suppressor functions in prostate cancer. / Haldrup, Jakob; Strand, Siri H.; Cieza-Borrella, Clara; Jakobsson, Magnus E.; Riedel, Maria; Norgaard, Maibritt; Hedensted, Stine; Dagnaes-Hansen, Frederik; Ulhoi, Benedicte Parm; Eeles, Rosalind; Borre, Michael; Olsen, Jesper; Thomsen, Martin; Kote-Jarai, Zsofia; Sorensen, Karina D.

In: Oncogene, Vol. 40, 2021, p. 763-776.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Haldrup, J, Strand, SH, Cieza-Borrella, C, Jakobsson, ME, Riedel, M, Norgaard, M, Hedensted, S, Dagnaes-Hansen, F, Ulhoi, BP, Eeles, R, Borre, M, Olsen, J, Thomsen, M, Kote-Jarai, Z & Sorensen, KD 2021, 'FRMD6 has tumor suppressor functions in prostate cancer', Oncogene, vol. 40, pp. 763-776. https://doi.org/10.1038/s41388-020-01548-w

APA

Haldrup, J., Strand, S. H., Cieza-Borrella, C., Jakobsson, M. E., Riedel, M., Norgaard, M., Hedensted, S., Dagnaes-Hansen, F., Ulhoi, B. P., Eeles, R., Borre, M., Olsen, J., Thomsen, M., Kote-Jarai, Z., & Sorensen, K. D. (2021). FRMD6 has tumor suppressor functions in prostate cancer. Oncogene, 40, 763-776. https://doi.org/10.1038/s41388-020-01548-w

Vancouver

Haldrup J, Strand SH, Cieza-Borrella C, Jakobsson ME, Riedel M, Norgaard M et al. FRMD6 has tumor suppressor functions in prostate cancer. Oncogene. 2021;40:763-776. https://doi.org/10.1038/s41388-020-01548-w

Author

Haldrup, Jakob ; Strand, Siri H. ; Cieza-Borrella, Clara ; Jakobsson, Magnus E. ; Riedel, Maria ; Norgaard, Maibritt ; Hedensted, Stine ; Dagnaes-Hansen, Frederik ; Ulhoi, Benedicte Parm ; Eeles, Rosalind ; Borre, Michael ; Olsen, Jesper ; Thomsen, Martin ; Kote-Jarai, Zsofia ; Sorensen, Karina D. / FRMD6 has tumor suppressor functions in prostate cancer. In: Oncogene. 2021 ; Vol. 40. pp. 763-776.

Bibtex

@article{0e0f0ff3122146d1ba3f0e805bba8fdc,
title = "FRMD6 has tumor suppressor functions in prostate cancer",
abstract = "Available tools for prostate cancer (PC) prognosis are suboptimal but may be improved by better knowledge about genes driving tumor aggressiveness. Here, we identified FRMD6 (FERM domain-containing protein 6) as an aberrantly hypermethylated and significantly downregulated gene in PC. Low FRMD6 expression was associated with postoperative biochemical recurrence in two large PC patient cohorts. In overexpression and CRISPR/Cas9 knockout experiments in PC cell lines, FRMD6 inhibited viability, proliferation, cell cycle progression, colony formation, 3D spheroid growth, and tumor xenograft growth in mice. Transcriptomic, proteomic, and phospho-proteomic profiling revealed enrichment of Hippo/YAP and c-MYC signaling upon FRMD6 knockout. Connectivity Map analysis and drug repurposing experiments identified pyroxamide as a new potential therapy for FRMD6 deficient PC cells. Finally, we established orthotropic Frmd6 and Pten, or Pten only (control) knockout in the ROSA26 mouse prostate. After 12 weeks, Frmd6/Pten double knockouts presented high-grade prostatic intraepithelial neoplasia (HG-PIN) and hyperproliferation, while Pten single-knockouts developed only regular PIN lesions and displayed lower proliferation. In conclusion, FRMD6 was identified as a novel tumor suppressor gene and prognostic biomarker candidate in PC.",
keywords = "EXPRESSION ANALYSIS, GENE, YAP/TAZ, TOPHAT, WILLIN",
author = "Jakob Haldrup and Strand, {Siri H.} and Clara Cieza-Borrella and Jakobsson, {Magnus E.} and Maria Riedel and Maibritt Norgaard and Stine Hedensted and Frederik Dagnaes-Hansen and Ulhoi, {Benedicte Parm} and Rosalind Eeles and Michael Borre and Jesper Olsen and Martin Thomsen and Zsofia Kote-Jarai and Sorensen, {Karina D.}",
year = "2021",
doi = "10.1038/s41388-020-01548-w",
language = "English",
volume = "40",
pages = "763--776",
journal = "Oncogene",
issn = "0950-9232",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - FRMD6 has tumor suppressor functions in prostate cancer

AU - Haldrup, Jakob

AU - Strand, Siri H.

AU - Cieza-Borrella, Clara

AU - Jakobsson, Magnus E.

AU - Riedel, Maria

AU - Norgaard, Maibritt

AU - Hedensted, Stine

AU - Dagnaes-Hansen, Frederik

AU - Ulhoi, Benedicte Parm

AU - Eeles, Rosalind

AU - Borre, Michael

AU - Olsen, Jesper

AU - Thomsen, Martin

AU - Kote-Jarai, Zsofia

AU - Sorensen, Karina D.

PY - 2021

Y1 - 2021

N2 - Available tools for prostate cancer (PC) prognosis are suboptimal but may be improved by better knowledge about genes driving tumor aggressiveness. Here, we identified FRMD6 (FERM domain-containing protein 6) as an aberrantly hypermethylated and significantly downregulated gene in PC. Low FRMD6 expression was associated with postoperative biochemical recurrence in two large PC patient cohorts. In overexpression and CRISPR/Cas9 knockout experiments in PC cell lines, FRMD6 inhibited viability, proliferation, cell cycle progression, colony formation, 3D spheroid growth, and tumor xenograft growth in mice. Transcriptomic, proteomic, and phospho-proteomic profiling revealed enrichment of Hippo/YAP and c-MYC signaling upon FRMD6 knockout. Connectivity Map analysis and drug repurposing experiments identified pyroxamide as a new potential therapy for FRMD6 deficient PC cells. Finally, we established orthotropic Frmd6 and Pten, or Pten only (control) knockout in the ROSA26 mouse prostate. After 12 weeks, Frmd6/Pten double knockouts presented high-grade prostatic intraepithelial neoplasia (HG-PIN) and hyperproliferation, while Pten single-knockouts developed only regular PIN lesions and displayed lower proliferation. In conclusion, FRMD6 was identified as a novel tumor suppressor gene and prognostic biomarker candidate in PC.

AB - Available tools for prostate cancer (PC) prognosis are suboptimal but may be improved by better knowledge about genes driving tumor aggressiveness. Here, we identified FRMD6 (FERM domain-containing protein 6) as an aberrantly hypermethylated and significantly downregulated gene in PC. Low FRMD6 expression was associated with postoperative biochemical recurrence in two large PC patient cohorts. In overexpression and CRISPR/Cas9 knockout experiments in PC cell lines, FRMD6 inhibited viability, proliferation, cell cycle progression, colony formation, 3D spheroid growth, and tumor xenograft growth in mice. Transcriptomic, proteomic, and phospho-proteomic profiling revealed enrichment of Hippo/YAP and c-MYC signaling upon FRMD6 knockout. Connectivity Map analysis and drug repurposing experiments identified pyroxamide as a new potential therapy for FRMD6 deficient PC cells. Finally, we established orthotropic Frmd6 and Pten, or Pten only (control) knockout in the ROSA26 mouse prostate. After 12 weeks, Frmd6/Pten double knockouts presented high-grade prostatic intraepithelial neoplasia (HG-PIN) and hyperproliferation, while Pten single-knockouts developed only regular PIN lesions and displayed lower proliferation. In conclusion, FRMD6 was identified as a novel tumor suppressor gene and prognostic biomarker candidate in PC.

KW - EXPRESSION ANALYSIS

KW - GENE

KW - YAP/TAZ

KW - TOPHAT

KW - WILLIN

U2 - 10.1038/s41388-020-01548-w

DO - 10.1038/s41388-020-01548-w

M3 - Journal article

C2 - 33249427

VL - 40

SP - 763

EP - 776

JO - Oncogene

JF - Oncogene

SN - 0950-9232

ER -

ID: 253447541