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Nat Commun. 2017 Oct 20;8(1):1081. doi: 10.1038/s41467-017-01198-9.

Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in prostate oncogenesis.

Author information

1
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
2
Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
3
Department of Urology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
4
Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA. sawyersc@mskcc.org.

Abstract

A multigenic locus at 3p13-14, spanning FOXP1 to SHQ1, is commonly deleted in prostate cancer and lost broadly in a range of cancers but has unknown significance to oncogenesis or prognosis. Here, we report that FOXP1-SHQ1 deletion cooperates with PTEN loss to accelerate prostate oncogenesis and that loss of component genes correlates with prostate, breast, and head and neck cancer recurrence. We demonstrate that Foxp1-Shq1 deletion accelerates prostate tumorigenesis in mice in combination with Pten loss, consistent with the association of FOXP1-SHQ1 and PTEN loss observed in human cancers. Tumors with combined Foxp1-Shq1 and Pten deletion show increased proliferation and anaplastic dedifferentiation, as well as mTORC1 hyperactivation with reduced Akt phosphorylation. Foxp1-Shq1 deletion restores expression of AR target genes repressed in tumors with Pten loss, circumventing PI3K-mediated repression of the androgen axis. Moreover, FOXP1-SHQ1 deletion has prognostic relevance, with cancer recurrence associated with combined loss of PTEN and FOXP1-SHQ1 genes.

PMID:
29057879
PMCID:
PMC5651901
DOI:
10.1038/s41467-017-01198-9
[Indexed for MEDLINE]
Free PMC Article

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