An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer

Cancer Research
Xin LuYuzhuo Wang

Abstract

Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen. Among the top positive hits, we conducted an in-depth functional analysis on Pygopus family PHD finger 2 (PYGO2), located in the amplicon at 1q21.3. PYGO2 overexpression enhances primary tumor growth and local invasion to draining lymph nodes. Conversely, PYGO2 depletion inhibits prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impairs tumor progression. Finally, PYGO2 is necessary to enhance the transcriptional activation in response to ligand-induced Wnt/β-cateni...Continue Reading

References

Jul 6, 2000·Laboratory Investigation; a Journal of Technical Methods and Pathology·J C AlersH van Dekken
Apr 18, 2003·Current Biology : CB·Michael T VeemanRandall T Moon
Jan 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jacques LapointeJonathan R Pollack
Apr 8, 2004·Neoplasia : an International Journal for Oncology Research·Daniel R RhodesArul M Chinnaiyan
Jul 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yan Ping YuJian-Hua Luo
Dec 18, 2004·Cancer Research·Raanan BergerWilliam C Hahn
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rameen BeroukhimWilliam R Sellers
Nov 26, 2008·European Journal of Pharmacology·Wenyan LuYonghe Li
Dec 25, 2008·Neoplasia : an International Journal for Oncology Research·Zhong WuDan Theodorescu
Jun 3, 2009·The Journal of Cell Biology·Valerie Horsley
Jun 29, 2010·Cancer Cell·Barry S TaylorWilliam L Gerald
Dec 14, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Vassiliki TzelepiAna M Aparicio
May 23, 2012·Nature Genetics·Christopher E BarbieriLevi A Garraway
Jun 23, 2012·Nature·Catherine S GrassoScott A Tomlins
Apr 12, 2013·Cancer Research·Feng YangDavid R Rowley
Apr 30, 2013·Cell·Sylvan C BacaLevi A Garraway
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
May 14, 2014·Nature Reviews. Clinical Oncology·Benjamin A Gartrell, Fred Saad
May 23, 2015·Cell·Dan RobinsonArul M Chinnaiyan
Nov 7, 2015·Cell·UNKNOWN Cancer Genome Atlas Research Network
Feb 9, 2016·Nature Medicine·Himisha BeltranFrancesca Demichelis
Apr 29, 2016·Science·Samra Turajlic, Charles Swanton
Jan 6, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Sep 13, 2017·Nature Reviews. Urology·Virginia Murillo-Garzón, Robert Kypta

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