SRPK1 inhibition in prostate cancer: A novel anti-angiogenic treatment through modulation of VEGF alternative splicing

Mavrou, Athina; Oltean, Sebastian

doi:10.1016/j.phrs.2016.03.013

Cited by 26 publications

(29 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To date, SRPK1 has been shown to be overexpressed in different types of cancers, and several mechanisms were reported to be responsible for its oncogenic role. SRPK1 could regulate VEGF splicing through phosphorylation of the splice factor SRSF1 and thus promote tumor angiogenesis of prostate cancers (Bullock et al, 2016;Mavrou & Oltean, 2016;Morooka et al, 2015), some studies also showed that SRPK1 can promote Akt phosphorylation to affect cell proliferation of hepatocellular carcinomas and contribute to GC whole-transcript expression analysis for SRPK1 knockdown cells, we found a majority of snoRNAs were decreased with SRPK1 silencing.…”

Section: Discussionsupporting

confidence: 50%

SRPK1 facilitates tumor cell growth via modulating the small nucleolar RNA expression in gastric cancer

Wang

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Serine‐arginine protein kinase 1 (SRPK1) is the main regulator in alternative splicing by phosphorylating splicing factors rich in serine/arginine repeats. Its overexpression has been found in multiple cancer types and contributes to cancer development. Here we report the role of SRPK1 and underlying mechanism in gastric cancer (GC) cell growth. We found that SRPK1 was frequently upregulated in GC samples compared with their adjacent corresponding normal tissues by immunohistochemistry and western blot analysis. Knockdown of SRPK1 in GC cells suppressed cell growth in cell viability assays, colony formation assays and nude mice xenograft model, whereas overexpression of SRPK1 promotes opposite phenotypes in these assays. By a complementary DNA microarray analysis, we found that SRPK1 knockdown had significant inhibitory effects on a majority of small nucleolar RNAs expression. Among them, snoRA42, snoRA74A, and snoRD10 were selected for further functional experiments. Cell growth curves on a plate and in soft agar indicated that the three snoRNAs play potential oncogenic function in GC. In addition, SRPK1 could co‐immunoprecipitated with NCL, a nucleolar phosphoprotein involved in the synthesis and maturation of ribosomes. These results suggested that SRPK1 contributes to GC development by a new possible mechanism involving snoRNAs mediated signaling.

show abstract

Section: Discussionsupporting

confidence: 50%

SRPK1 facilitates tumor cell growth via modulating the small nucleolar RNA expression in gastric cancer

Wang

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…SRPK1 expression increases in prostate cancer (Bullock and Oltean 2016 ; Bullock et al 2016 ; Mavrou et al 2015 ). Existing drugs are available that can target SRPK1 and have already been tested in mouse models (Mavrou et al 2015 ; Mavrou and Oltean 2016 ). A further important kinase that might impact on prostate cancer pathology is aurora A, which affects the production of ARv splice variants, likely also through control of SRSF1 (Jones et al 2017 ).…”

Section: Splicing Regulators Can Change Expression Patterns In Prostamentioning

confidence: 99%

RNA splicing and splicing regulator changes in prostate cancer pathology

et al. 2017

View full text Add to dashboard Cite

Changes in mRNA splice patterns have been associated with key pathological mechanisms in prostate cancer progression. The androgen receptor (abbreviated AR) transcription factor is a major driver of prostate cancer pathology and activated by androgen steroid hormones. Selection of alternative promoters by the activated AR can critically alter gene function by switching mRNA isoform production, including creating a pro-oncogenic isoform of the normally tumour suppressor gene TSC2. A number of androgen-regulated genes generate alternatively spliced mRNA isoforms, including a prostate-specific splice isoform of ST6GALNAC1 mRNA. ST6GALNAC1 encodes a sialyltransferase that catalyses the synthesis of the cancer-associated sTn antigen important for cell mobility. Genetic rearrangements occurring early in prostate cancer development place ERG oncogene expression under the control of the androgen-regulated TMPRSS2 promoter to hijack cell behaviour. This TMPRSS2–ERG fusion gene shows different patterns of alternative splicing in invasive versus localised prostate cancer. Alternative AR mRNA isoforms play a key role in the generation of prostate cancer drug resistance, by providing a mechanism through which prostate cancer cells can grow in limited serum androgen concentrations. A number of splicing regulator proteins change expression patterns in prostate cancer and may help drive key stages of disease progression. Up-regulation of SRRM4 establishes neuronal splicing patterns in neuroendocrine prostate cancer. The splicing regulators Sam68 and Tra2β increase expression in prostate cancer. The SR protein kinase SRPK1 that modulates the activity of SR proteins is up-regulated in prostate cancer and has already given encouraging results as a potential therapeutic target in mouse models.

show abstract

“…Analogically, ERK may also regulate the phosphorylation and functions of SRPK1, but this will need more evidence to verify. Besides ERK and AKT, SRPK1 can activate several other tumor-related proteins in distinct tumor types, such as JNK [ 27 ] and VEGFs [ 28 – 30 ]. Certain up-stream regulators for SRPK1 were also identified, including RhoA [ 31 ], Wnt [ 15 ], TGF-β [ 27 ], long non-coding RNAs [ 25 ] and human papillomavirus type 1 E1^E4 protein [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Serine-arginine protein kinase 1 (SRPK1) is elevated in gastric cancer and plays oncogenic functions

Wei

Wang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Serine-arginine protein kinase 1 (SRPK1) phosphorylates proteins involved in the regulation of several mRNA processing pathways including alternative splicing. SRPK1 has been reported to be over-expressed in multiple cancers including prostate, breast, lung and glioma. Several studies further identified that inhibition of SRPK1 showed tumor-suppressive effects, thus raising SRPK1 as a novel candidate chemotherapy target. Interestingly, SRPK1 plays tumor suppressing role in mouse embryonic fibroblasts, on that SRPK1-silencing induces cell transformation. Therefore, the effect of SRPK1 seems heterogeneously in different cell types and tissues. The existence and role of SRPK1 in gastric cancer (GC) hasn’t been reported. Here we investigated the expression pattern of SRPK1 in GC by immunohistochemistry and found that it was up-regulated in tumor tissues, where its expression was correlated with tumor grade and prognosis. Further, we explored the signaling mechanism of SRPK1 in promoting GC progression, which revealed that both PP2A and DUSP6 phosphatases impaired the oncogenic effects of SRPK1. However, we didn’t find any direct interaction between SRPK1 with PP2A or DUSP6, indicating PP2A and DUSP6 function by regulating the downstream effectors of SRPK1. Our study not only revealed the clinical significance of SRPK1 in GC, but also provided new evidence for its signaling modulation which is invaluable for novel chemotherapy development.

show abstract

SRPK1 inhibition in prostate cancer: A novel anti-angiogenic treatment through modulation of VEGF alternative splicing

Abstract: Graphical abstract

Cited by 26 publications

References 38 publications

SRPK1 facilitates tumor cell growth via modulating the small nucleolar RNA expression in gastric cancer

SRPK1 facilitates tumor cell growth via modulating the small nucleolar RNA expression in gastric cancer

RNA splicing and splicing regulator changes in prostate cancer pathology

Serine-arginine protein kinase 1 (SRPK1) is elevated in gastric cancer and plays oncogenic functions

Contact Info

Product

Resources

About