Coordinate loss of MAP3K7 and CHD1 promotes aggressive prostate cancer

Cancer Research
Lindsey Ulkus RodriguesScott D Cramer

Abstract

Prostate cancer subtypes are poorly defined and functional validation of drivers of ETS rearrangement-negative prostate cancer has not been conducted. Here, we identified an ETS(-) subtype of aggressive prostate cancer (ERG(-)MAP3K7(del)CHD1(del)) and used a novel developmental model and a cell line xenograft model to show that cosuppression of MAP3K7 and CHD1 expression promotes aggressive disease. Analyses of publicly available prostate cancer datasets revealed that MAP3K7 and CHD1 were significantly codeleted in 10% to 20% of localized tumors and combined loss correlated with poor disease-free survival. To evaluate the functional impact of dual MAP3K7-CHD1 loss, we suppressed Map3k7 and/or Chd1 expression in mouse prostate epithelial progenitor/stem cells (PrP/SC) and performed tissue recombination experiments in vivo. Dual shMap3k7-shChd1 PrP/SC recombinants displayed massive glandular atypia with regions of prostatic intraepithelial neoplasia and carcinoma apparent. Combined Map3k7-Chd1 suppression greatly disrupted normal prostatic lineage differentiation; dual recombinants displayed significant androgen receptor loss, increased neuroendocrine differentiation, and increased neural differentiation. Clinical samples with du...Continue Reading

References

Jan 28, 2003·Journal of Molecular Biology·Giichi TakaesuRichard B Gaynor
Dec 16, 2004·The Prostate·Wendy W Barclay, Scott D Cramer
Sep 28, 2005·Nature Immunology·Shintaro SatoShizuo Akira
Dec 24, 2005·Nature·John F FlanaganSepideh Khorasanizadeh
Sep 6, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wennuan LiuJianfeng Xu
Jun 10, 2008·Cancer Cell·Scott A TomlinsArul M Chinnaiyan
Apr 28, 2009·Nature Genetics·Jennifer C KingCharles L Sawyers
Jul 10, 2009·Nature·Alexandre Gaspar-MaiaMiguel Ramalho-Santos
Jul 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yang ZongOwen N Witte
Jun 29, 2010·Cancer Cell·Barry S TaylorWilliam L Gerald
Feb 11, 2011·Nature·Michael F BergerLevi A Garraway
Apr 3, 2012·Cancer Research·Min WuScott D Cramer
May 23, 2012·Nature Genetics·Christopher E BarbieriLevi A Garraway
Jun 23, 2012·Nature·Catherine S GrassoScott A Tomlins
Feb 2, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Martina KluthSarah Minner
Mar 16, 2013·Cancer Research·Lia BurkhardtRonald Simon
Apr 4, 2013·Science Signaling·Jianjiong GaoNikolaus Schultz
Apr 30, 2013·Cell·Sylvan C BacaLevi A Garraway
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Feb 25, 2014·Neoplasia : an International Journal for Oncology Research·Mirjam BlattnerMark A Rubin

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Citations

Nov 7, 2015·Cell·UNKNOWN Cancer Genome Atlas Research Network
May 25, 2016·Developmental Cell·Megan L GoodallAndrew Thorburn
Jul 23, 2016·Nature Reviews. Drug Discovery·Timothy A YapJohann S de Bono
Sep 7, 2016·Journal of Molecular Biology·Biswaranjan MohantyDaniel P Ryan
Aug 31, 2016·Cell Cycle·Megan L GoodallAndrew Thorburn
Jun 22, 2017·Expert Review of Molecular Diagnostics·Minke SmitsJack A Schalken
May 10, 2017·International Journal of Molecular Sciences·Simon J Baumgart, Bernard Haendler
Apr 25, 2018·International Journal of Molecular Sciences·Shyh-Han TanShiv Srivastava
Oct 28, 2015·ELife·Leah Rider, Scott D Cramer
Jan 10, 2019·Genes, Chromosomes & Cancer·Martina KluthWaldemar Wilczak
Apr 21, 2017·Oncotarget·Weerachai JaratlerdsiriVanessa M Hayes
Jul 28, 2016·Oncotarget·Megan L GoodallAndrew Thorburn
Dec 25, 2019·Signal Transduction and Targeted Therapy·Yuan ChengXiawei Wei
Mar 7, 2020·Science Translational Medicine·Mitchell G LawrenceGail P Risbridger
Jun 12, 2018·Current Molecular Biology Reports·Katia RuggeroAlvaro Aytes
Mar 24, 2020·British Journal of Cancer·Bogdan-Alexandru LucaColin S Cooper
Feb 14, 2018·Cancer Immunology Research·Colleen S CurranElad Sharon
Oct 20, 2018·Molecular Cancer Research : MCR·Habiba ElfandyMassimo Loda
Jul 30, 2019·Trends in Molecular Medicine·Vipul Bhatia, Bushra Ateeq
Nov 18, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Diana C DeLuciaJohn K Lee
Dec 17, 2020·Signal Transduction and Targeted Therapy·Yuan ChengXiawei Wei
Jun 11, 2020·Trends in Cancer·Susanne Burdak-RothkammKai Rothkamm
Mar 13, 2021·Molecular Cancer Research : MCR·Natasa BroitAntonia L Pritchard
Jun 17, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Mariana Brütt PachecoCarmen Jerónimo
Jul 3, 2021·Cancers·Lauren K JillsonScott D Cramer

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