Identification of potential therapeutic targets in prostate cancer through a cross‐species approach
Abstract Genetically engineered mouse models of cancer can be used to filter genome‐wide expression datasets generated from human tumours and to identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNAseq data fr...
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doaj-f4f3abda48f3447a8e0ee97abf3bc7cf2021-08-02T12:19:01ZengWileyEMBO Molecular Medicine1757-46761757-46842018-03-01103n/an/a10.15252/emmm.201708274Identification of potential therapeutic targets in prostate cancer through a cross‐species approachSarah Jurmeister0Antonio Ramos‐Montoya1Chiranjeevi Sandi2Nelma Pértega‐Gomes3Karan Wadhwa4Alastair D Lamb5Mark J Dunning6Jan Attig7Jason S Carroll8Lee GD Fryer9Sérgio L Felisbino10David E Neal11Uro‐oncology Research Group CRUK Cambridge Institute Cambridge UKUro‐oncology Research Group CRUK Cambridge Institute Cambridge UKUro‐oncology Research Group CRUK Cambridge Institute Cambridge UKDepartment of Medical Oncology Dana‐Farber Cancer Institute Harvard Medical School Boston MA USAUro‐oncology Research Group CRUK Cambridge Institute Cambridge UKUro‐oncology Research Group CRUK Cambridge Institute Cambridge UKBioinformatics Core Facility CRUK Cambridge Institute Cambridge UKDepartment of Molecular Neuroscience UCL Institute of Neurology London UKCancer Research UK Cambridge Institute University of Cambridge Cambridge UKUro‐oncology Research Group CRUK Cambridge Institute Cambridge UKDepartment of Morphology Institute of Biosciences of Botucatu Sao Paulo State University (UNESP) Sao Paulo BrazilUro‐oncology Research Group CRUK Cambridge Institute Cambridge UKAbstract Genetically engineered mouse models of cancer can be used to filter genome‐wide expression datasets generated from human tumours and to identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNAseq data from tumours arising in two established mouse models of prostate cancer, PB‐Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer‐associated gene expression changes that are conserved between the two species. To identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we revealed a functional role for the kinase MELK as a driver and potential therapeutic target in prostate cancer. We found that MELK expression was required for cell survival, affected the expression of genes associated with prostate cancer progression and was associated with biochemical recurrence.https://doi.org/10.15252/emmm.201708274cross‐species analysisMELKmouse modelsnew cancer targetsprostate cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sarah Jurmeister Antonio Ramos‐Montoya Chiranjeevi Sandi Nelma Pértega‐Gomes Karan Wadhwa Alastair D Lamb Mark J Dunning Jan Attig Jason S Carroll Lee GD Fryer Sérgio L Felisbino David E Neal |
spellingShingle |
Sarah Jurmeister Antonio Ramos‐Montoya Chiranjeevi Sandi Nelma Pértega‐Gomes Karan Wadhwa Alastair D Lamb Mark J Dunning Jan Attig Jason S Carroll Lee GD Fryer Sérgio L Felisbino David E Neal Identification of potential therapeutic targets in prostate cancer through a cross‐species approach EMBO Molecular Medicine cross‐species analysis MELK mouse models new cancer targets prostate cancer |
author_facet |
Sarah Jurmeister Antonio Ramos‐Montoya Chiranjeevi Sandi Nelma Pértega‐Gomes Karan Wadhwa Alastair D Lamb Mark J Dunning Jan Attig Jason S Carroll Lee GD Fryer Sérgio L Felisbino David E Neal |
author_sort |
Sarah Jurmeister |
title |
Identification of potential therapeutic targets in prostate cancer through a cross‐species approach |
title_short |
Identification of potential therapeutic targets in prostate cancer through a cross‐species approach |
title_full |
Identification of potential therapeutic targets in prostate cancer through a cross‐species approach |
title_fullStr |
Identification of potential therapeutic targets in prostate cancer through a cross‐species approach |
title_full_unstemmed |
Identification of potential therapeutic targets in prostate cancer through a cross‐species approach |
title_sort |
identification of potential therapeutic targets in prostate cancer through a cross‐species approach |
publisher |
Wiley |
series |
EMBO Molecular Medicine |
issn |
1757-4676 1757-4684 |
publishDate |
2018-03-01 |
description |
Abstract Genetically engineered mouse models of cancer can be used to filter genome‐wide expression datasets generated from human tumours and to identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNAseq data from tumours arising in two established mouse models of prostate cancer, PB‐Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer‐associated gene expression changes that are conserved between the two species. To identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we revealed a functional role for the kinase MELK as a driver and potential therapeutic target in prostate cancer. We found that MELK expression was required for cell survival, affected the expression of genes associated with prostate cancer progression and was associated with biochemical recurrence. |
topic |
cross‐species analysis MELK mouse models new cancer targets prostate cancer |
url |
https://doi.org/10.15252/emmm.201708274 |
work_keys_str_mv |
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