PMID- 25381816
OWN - NLM
STAT- MEDLINE
DCOM- 20151029
LR  - 20220321
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 34
IP  - 33
DP  - 2015 Aug 13
TI  - Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted 
      therapeutic strategy in prostate cancer.
PG  - 4311-9
LID - 10.1038/onc.2014.360 [doi]
AB  - Angiogenesis is required for tumour growth and is induced principally by vascular 
      endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at 
      the terminal exon to produce two families of isoforms, pro- and anti-angiogenic, 
      only the former of which is upregulated in prostate cancer (PCa). In renal 
      epithelial cells and colon cancer cells, the choice of VEGF splice isoforms is 
      controlled by the splicing factor SRSF1, phosphorylated by serine-arginine 
      protein kinase 1 (SRPK1). Immunohistochemistry staining of human samples revealed 
      a significant increase in SRPK1 expression both in prostate intra-epithelial 
      neoplasia lesions as well as malignant adenocarcinoma compared with benign 
      prostate tissue. We therefore tested the hypothesis that the selective 
      upregulation of pro-angiogenic VEGF in PCa may be under the control of SRPK1 
      activity. A switch in the expression of VEGF165 towards the anti-angiogenic 
      splice isoform, VEGF165b, was seen in PC-3 cells with SRPK1 knockdown (KD). PC-3 
      SRPK1-KD cells resulted in tumours that grew more slowly in xenografts, with 
      decreased microvessel density. No effect was seen as a result of SRPK1-KD on 
      growth, proliferation, migration and invasion capabilities of PC-3 cells in 
      vitro. Small-molecule inhibitors of SRPK1 switched splicing towards the 
      anti-angiogenic isoform VEGF165b in PC-3 cells and decreased tumour growth when 
      administered intraperitoneally in an orthotopic mouse model of PCa. Our study 
      suggests that modulation of SRPK1 and subsequent inhibition of tumour 
      angiogenesis by regulation of VEGF splicing can alter prostate tumour growth and 
      supports further studies for the use of SRPK1 inhibition as a potential 
      anti-angiogenic therapy in PCa.
FAU - Mavrou, A
AU  - Mavrou A
AD  - School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
FAU - Brakspear, K
AU  - Brakspear K
AD  - School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
FAU - Hamdollah-Zadeh, M
AU  - Hamdollah-Zadeh M
AD  - School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
FAU - Damodaran, G
AU  - Damodaran G
AD  - School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
FAU - Babaei-Jadidi, R
AU  - Babaei-Jadidi R
AD  - Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University 
      of Nottingham, Nottingham, UK.
FAU - Oxley, J
AU  - Oxley J
AD  - Department of Cellular Pathology, North Bristol NHS Trust, Bristol, UK.
FAU - Gillatt, D A
AU  - Gillatt DA
AD  - Department of Urological Sciences, North Bristol NHS Trust, Bristol, UK.
FAU - Ladomery, M R
AU  - Ladomery MR
AD  - Centre for Research in Bioscience, Faculty of Health and Applied Sciences, 
      University of the West of England, Bristol, UK.
FAU - Harper, S J
AU  - Harper SJ
AD  - School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
FAU - Bates, D O
AU  - Bates DO
AD  - 1] School of Physiology and Pharmacology, University of Bristol, Bristol, UK [2] 
      Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University 
      of Nottingham, Nottingham, UK.
FAU - Oltean, S
AU  - Oltean S
AD  - School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
LA  - eng
GR  - C11392/A10484/Cancer Research UK/United Kingdom
GR  - G1002073/MRC_/Medical Research Council/United Kingdom
GR  - BB/J007293/1/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - MR/K020366/1/MRC_/Medical Research Council/United Kingdom
GR  - G10002073/Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141110
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Protein Isoforms)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.1.- (SRPK1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Invasiveness/pathology
MH  - Neovascularization, Pathologic/drug therapy/metabolism
MH  - Prostatic Neoplasms/*drug therapy/*metabolism/pathology
MH  - Protein Isoforms/metabolism
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors/*metabolism
MH  - RNA Splicing/drug effects
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC4351909
MID - EMS60396
OID - NLM: EMS60396
EDAT- 2014/11/11 06:00
MHDA- 2015/10/30 06:00
PMCR- 2016/02/13
CRDT- 2014/11/11 06:00
PHST- 2014/04/21 00:00 [received]
PHST- 2014/07/31 00:00 [revised]
PHST- 2014/09/16 00:00 [accepted]
PHST- 2014/11/11 06:00 [entrez]
PHST- 2014/11/11 06:00 [pubmed]
PHST- 2015/10/30 06:00 [medline]
PHST- 2016/02/13 00:00 [pmc-release]
AID - 10.1038/onc.2014.360 [doi]
PST - ppublish
SO  - Oncogene. 2015 Aug 13;34(33):4311-9. doi: 10.1038/onc.2014.360. Epub 2014 Nov 10.