Professor of Genetics ,Centre for Research in Biosciences Department of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol, UK
TTARGETING PROSTATE CANCER CELLS
THROUGH SPLICING – TWO CASE STUDIESBC
Host: M. Baralle
Abstract
The purpose of this seminar is to present the results of two projects aimed at exploring the potential of manipulating splicing in prostate cancer cells. (1) In the first approach, we targeted splice factor kinases, specifically the CLKs, using the benzothiazole TG003. CLK inhibition significantly reduced proliferation, cell migration, and increased apoptosis. The growth of PC3 prostate cancer cells was severely curtailed by TG003 in mouse xenografts. CLK inhibition by TG003 correlated with consistent changes in the alternative splicing of several cancer-associated genes. (2) In the second approach, we focused on the ERG oncogene, encoding a transcription factor, that is activated in a significant proportion of men with prostate cancer. The approach was to use an antisense approach to target both cassette exon 7b and constitutive exon 4 with splice-switching oligonucleotides (SSOs). The SSOs were able to cause significant knockdown of ERG expression and activity, reducing the viability of prostate cancer cells. Together, both these approaches highlight the utility of targeting splicing in prostate cancer, and in cancer more widely.
International Seminar Programme
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