Serine-Arginine Protein Kinase 1 (SRPK1): a systematic review of its multimodal role in oncogenesis

Duggan, William; OʼConnell, Emer; Prehn, Jochen H M; Burke, John P.

doi:10.1007/s11010-022-04456-7

Cited by 6 publications

(10 citation statements)

References 87 publications

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“…Current approaches to exploiting SRPK, CLK and DYRK kinase families for therapy SRPK, CLK, DYRK, and sub-family HIPK have been associated with several disease indications, with potential therapeutic strategies either discussed or being pursued. Disease areas include viral infection and replication [193,[281][282][283][284], tumour angiogenesis [285,286], and other aspects of tumour growth and biology [2,113,[287][288][289]. The diverse roles of DYRKs in cancer have been extensively reviewed elsewhere [126,[290][291][292][293].…”

Section: Therapeutic Potential Of Srpk Clk and Dyrk Kinase Families I...mentioning

confidence: 99%

Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders

Hogg,

Findlay

2023

FEBS Letters

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Human developmental disorders encompass a wide range of debilitating physical conditions and intellectual disabilities. Perturbation of protein kinase signalling underlies the development of some of these disorders. For example, disrupted SRPK signalling is associated with intellectual disabilities, and the gene dosage of DYRKs can dictate the pathology of disorders including Down's syndrome. Here, we review the emerging roles of the CMGC kinase families SRPK, CLK, DYRK, and sub‐family HIPK during embryonic development and in developmental disorders. In particular, SRPK, CLK, and DYRK kinase families have key roles in developmental signalling and stem cell regulation, and can co‐ordinate neuronal development and function. Genetic studies in model organisms reveal critical phenotypes including embryonic lethality, sterility, musculoskeletal errors, and most notably, altered neurological behaviours arising from defects of the neuroectoderm and altered neuronal signalling. Further unpicking the mechanisms of specific kinases using human stem cell models of neuronal differentiation and function will improve our understanding of human developmental disorders and may provide avenues for therapeutic strategies.

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Section: Therapeutic Potential Of Srpk Clk and Dyrk Kinase Families I...mentioning

confidence: 99%

Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders

Hogg,

Findlay

2023

FEBS Letters

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“…These genes play important roles in the occurrence and development of tumors, and the abnormal activity of SRPK1 may affect the function of these genes. Research has found that SRPK1 is aberrantly expressed in both the tissue and cells of gliomas, while no abnormal expression has been observed in normal glioma cells [21]. Silencing SRPK1 has been shown to induce cisplatin resistance [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…Research has found that SRPK1 is aberrantly expressed in both the tissue and cells of gliomas, while no abnormal expression has been observed in normal glioma cells [21]. Silencing SRPK1 has been shown to induce cisplatin resistance [21,22]. Under normoxic and moderately hypoxic conditions, knocking down SRPK1 inhibits the malignant progression of glioma cells [21,22], induces apoptosis in glioma cells [21,23], and suppresses AKT/E1F4E phosphorylation [21].…”

Section: Introductionmentioning

confidence: 99%

“…Silencing SRPK1 has been shown to induce cisplatin resistance [21,22]. Under normoxic and moderately hypoxic conditions, knocking down SRPK1 inhibits the malignant progression of glioma cells [21,22], induces apoptosis in glioma cells [21,23], and suppresses AKT/E1F4E phosphorylation [21]. Plexin B1 promotes SRPK1 activity through the PI3K/AKT signaling pathway, thereby increasing cell growth, angiogenesis, and motility in vitro and in vivo [21,24].…”

Section: Introductionmentioning

confidence: 99%

“…Under normoxic and moderately hypoxic conditions, knocking down SRPK1 inhibits the malignant progression of glioma cells [21,22], induces apoptosis in glioma cells [21,23], and suppresses AKT/E1F4E phosphorylation [21]. Plexin B1 promotes SRPK1 activity through the PI3K/AKT signaling pathway, thereby increasing cell growth, angiogenesis, and motility in vitro and in vivo [21,24]. However, the specific mechanism by which SRPK1 regulates glioma cell proliferation remains unclear, and there is still an urgent need to continue exploring SRPK1-related signaling pathways in gliomas to find new therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

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SRPK1 Promotes Glioma Proliferation, Migration, and Invasion through Activation of Wnt/β-Catenin and JAK-2/STAT-3 Signaling Pathways

Shi,

Sun,

Deng

et al. 2024

Biomedicines

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Currently, the treatment of gliomas still relies primarily on surgery and radiochemotherapy. Although there are various drugs available, including temozolomide, the overall therapeutic effect is unsatisfactory, and the prognosis remains poor. Therefore, the in-depth study of the mechanism of glioma development and a search for new therapeutic targets are the keys to improving the therapeutic treatment of gliomas and improving the prognosis of patients. Immunohistochemistry is used to detect the expression of relevant molecules in tissues, qPCR and Western blot are used to detect the mRNA and protein expression of relevant molecules, CCK-8 (Cell Counting Kit-8) is used to assess cell viability and proliferation capacity, Transwell is used to evaluate cell migration and invasion ability, and RNA transcriptome sequencing is used to identify the most influential pathways. SRPK1 (SRSF protein kinase 1) is highly expressed in gliomas but is not expressed in normal tissues. Its expression is positively correlated with the grades of gliomas and negatively correlated with prognosis. SRPK1 significantly promotes the occurrence and development of gliomas. Knocking down SRPK1 leads to a significant decrease in the proliferation, migration, and invasion abilities of gliomas. Loss of SRPK1 expression induces G2/M phase arrest and mitotic catastrophe, leading to apoptosis in cells. Overexpression of SRPK1 activates the Wnt/β-catenin (wingless-int1/β-catenin) and JAK-2/STAT-3 (Janus kinase 2/signal transducer and activator of transcription 3) signaling pathways, promoting the proliferation, migration, and invasion of gliomas. Overexpression of SRPK1 rescues the reduced cell proliferation, migration, and invasion abilities caused by the silencing of β-catenin or JAK-2. A stable shRNA-LN229 cell line was constructed, and using a nude mouse model, it was found that stable knockout of SRPK1 significantly reduced the tumorigenic ability of glioma cells, as evidenced by a significant decrease in the subcutaneous tumor volume and weight in nude mice. We have demonstrated that SRPK1 is highly expressed in gliomas. Overexpression of SRPK1 activates the Wnt/β-catenin and JAK-2/STAT-3 signaling pathways, promoting the proliferation, migration, and invasion of gliomas. Silencing SRPK1-related signaling pathways may provide potential therapeutic options for glioma patients.

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CDK12‐inactivation‐induced MYC signaling causes dependency on the splicing kinase SRPK1

Liang,

Gondane,

Itkonen

2024

Molecular Oncology

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Inactivation of cyclin‐dependent kinase 12 (CDK12) characterizes an aggressive sub‐group of castration‐resistant prostate cancer (CRPC). Hyper‐activation of MYC transcription factor is sufficient to confer the CRPC phenotype. Here, we show that loss of CDK12 promotes MYC activity, which renders the cells dependent on the otherwise non‐essential splicing regulatory kinase SRSF protein kinase 1 (SRPK1). High MYC expression is associated with increased levels of SRPK1 in patient samples, and overexpression of MYC sensitizes prostate cancer cells to SRPK1 inhibition using pharmacological and genetic strategies. We show that Endovion (SCO‐101), a compound currently in clinical trials against pancreatic cancer, phenocopies the effects of the well‐characterized SRPK1 inhibitor SRPIN340 on nascent transcription. This is the first study to show that Endovion is an SRPK1 inhibitor. Inhibition of SRPK1 with either of the compounds promotes transcription elongation, and transcriptionally activates the unfolded protein response. In brief, here we discover that CDK12 inactivation promotes MYC signaling in an SRPK1‐dependent manner, and show that the clinical grade compound Endovion selectively targets the cells with CDK12 inactivation.

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Serine-Arginine Protein Kinase 1 (SRPK1): a systematic review of its multimodal role in oncogenesis

Cited by 6 publications

References 87 publications

Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders

Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders

SRPK1 Promotes Glioma Proliferation, Migration, and Invasion through Activation of Wnt/β-Catenin and JAK-2/STAT-3 Signaling Pathways

CDK12‐inactivation‐induced MYC signaling causes dependency on the splicing kinase SRPK1

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