Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in prostate oncogenesis Journal Article
| Authors: | Hieronymus, H.; Iaquinta, P. J.; Wongvipat, J.; Gopalan, A.; Murali, R.; Mao, N.; Carver, B. S.; Sawyers, C. L. |
| Article Title: | Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in prostate oncogenesis |
| 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. © 2017 The Author(s). |
| Keywords: | controlled study; major clinical study; gene deletion; mutation; androgen; cancer recurrence; nonhuman; endometrioid carcinoma; cell proliferation; animal cell; mouse; animal tissue; gene; mus; gene expression; embryo; embryonic stem cell; animal experiment; animal model; protein; gene locus; enzyme activity; phosphatidylinositol 3 kinase; kidney carcinoma; carcinogenesis; colorectal carcinoma; prostate cancer; lung adenocarcinoma; glioblastoma; breast carcinoma; gene repression; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; ovary carcinoma; gene loss; invasive carcinoma; prostate adenocarcinoma; clear cell carcinoma; tumor; transitional cell carcinoma; head and neck squamous cell carcinoma; cell dedifferentiation; genetic differentiation; cancer prognosis; cancer; human; male; article; prostate tissue; foxp1 gene; shq1 gene |
| Journal Title: | Nature Communications |
| Volume: | 8 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-10-20 |
| Start Page: | 1081 |
| Language: | English |
| DOI: | 10.1038/s41467-017-01198-9 |
| PROVIDER: | scopus |
| PMCID: | PMC5651901 |
| PUBMED: | 29057879 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 December 2017 -- Source: Scopus |
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