Journal
EMBO MOLECULAR MEDICINE
Volume 10, Issue 3, Pages -Publisher
WILEY
DOI: 10.15252/emmm.201708274
Keywords
cross-species analysis; MELK; mouse models; new cancer targets; prostate cancer
Categories
Funding
- Cancer Research UK project
- Sao Paulo Research Foundation (FAPESP) [2013/08830-2, 2013/06802-1]
- CNPq [305391/2014-3]
- Academy of Medical Sciences (AMS) [AMS-SGCL11-Lamb] Funding Source: researchfish
- Cancer Research UK [20411, 22310] Funding Source: researchfish
- Medical Research Council [MC_U105185858] Funding Source: researchfish
- National Institute for Health Research [CL-2012-14-003] Funding Source: researchfish
- MRC [MC_U105185858] Funding Source: UKRI
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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/Pten(loxP/loxP) and p53(loxP/loxP)Rb(loxP/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 thisapproach, 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.
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