Molecular Biology Reports

, Volume 46, Issue 1, pp 1487–1497 | Cite as

Serine arginine protein kinase 1 (SRPK1): a moonlighting protein with theranostic ability in cancer prevention

  • Mitesh Patel
  • Manojkumar Sachidanandan
  • Mohd AdnanEmail author


Serine/arginine protein kinase 1 (SRPK1); a versatile functional moonlighting protein involved in varied cellular activities comprised of cell cycle progression, innate immune response, chromatin reorganization, negative and positive regulation of viral genome replication, protein amino acid phosphorylation, regulation of numerous mRNA-processing pathways, germ cell development as well as inflammation due to acquaintances with many transcription factors and signaling pathways. Several diseases including cancer have been associated with dysregulation of SRPK1. The function of SRPK1 in cancer is contradictory and inexplicable because it acts as both tumor suppressor and promoter based on the type of cell and locale. Over expression of SRPK1 including its role has been recently narrated and associated with several cancers, which includes, lung, glioma, prostate and breast via dysregulated signals from the Akt/eIF4E/HIF-1/VEGF, Erk or MAPK, PI3K/AKT/mTOR, TGF-β, and Wnt/β-catenin signaling pathways. Therefore, SRPK1 has occurred as a promising and possible curative target in cancer. In recent years, few natural and synthetic SRPK1 inhibitors have been discovered. This review emphasizes and highlights the complicated connections between SRPK1 and oncogenic signaling circuits together with the possibility of aiming SRPK1 in the treatment of cancer.


Cancer SRPK1 Moonlighting proteins Oncogenic signaling Targeted therapy 



This work was supported by National Fellowship (Grant No.: NFO-2015-17-OBC-GUJ-29274) from University Grants Commission (UGC), New Delhi, India.

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest.


  1. 1.
    Giannakouros T, Nikolakaki E, Mylonis I et al (2011) Serine-arginine protein kinases: a small protein kinase family with a large cellular presence. FEBS J 278:570–586Google Scholar
  2. 2.
    Hatcher JM, Wu F, Zeng C et al (2018) SRPKIN-1: A covalent SRPK1/2 inhibitor that potently converts VEGF from pro-angiogenic to anti-angiogenic isoform. Cell Chem Biol 25:460–470.e6Google Scholar
  3. 3.
    Ma CT, Hagopian JC, Ghosh G et al (2009) Regiospecific phosphorylation control of the SR protein ASF/SF2 by SRPK1. J Mol Biol 390:618–634Google Scholar
  4. 4.
    Sellis D, Drosou V, Vlachakis D et al (2012) Phosphorylation of the arginine/serine repeats of lamin B receptor by SRPK1-insights from molecular dynamics simulations. Biochim Biophys Acta 1820:44–55Google Scholar
  5. 5.
    Hishizawa M, Imada K, Sakai T et al (2005) Serological identification of adult T-cell leukaemia-associated antigens. Br J Haematol 130:382–390Google Scholar
  6. 6.
    Papoutsopoulou S, Nikolakaki E, Chalepakis G et al (1999) SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1. Nucleic Acids Res 27:2972–2980Google Scholar
  7. 7.
    Salesse S, Dylla SJ, Verfaillie CM (2004) p210BCR/ABL-induced alteration of pre-mRNA splicing in primary human CD34+ hematopoietic progenitor cells. Leukemia 18:727–733Google Scholar
  8. 8.
    Hayes GM, Carrigan PE, Beck AM et al (2006) Targeting the RNA splicing machinery as a novel treatment strategy for pancreatic carcinoma. Cancer Res 3819–3827Google Scholar
  9. 9.
    Hayes GM, Carrigan PE, Miller LJ (2007) Serine-arginine protein kinase 1overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas. Cancer Res 67:2072–2080Google Scholar
  10. 10.
    Thorsen K, Mansilla F, Schepeler T et al (2011) Alternative splicing of SLC39A14 in colorectal cancer is regulated by the Wnt pathway. Mol Cell Prot 10:M110.002998Google Scholar
  11. 11.
    Odunsi K, Mhawech-Fauceglia P, Andrews C et al (2012) Elevated expression of the serine-arginine protein kinase 1 gene in ovarian cancer and its role in cisplatin cytotoxicity in vitro. PLoS ONE 7:e51030Google Scholar
  12. 12.
    Gout S, Brambilla E, Boudria A et al (2012) Abnormal expression of the pre-mRNA splicing regulators SRSF1, SRSF2, SRPK1 and SRPK2 in non small cell lung carcinoma. PLoS ONE 7:e46539Google Scholar
  13. 13.
    Jang SW, Yang SJ, Ehl´en A et al (2008) Serine/arginine protein specific kinase 2 promotes leukemia cell proliferation by phosphorylating acinus and regulating cyclin A1. Cancer Res 68:4559–4570Google Scholar
  14. 14.
    Zhou B, Li Y, Deng Q et al (2013) SRPK1 contributes to malignancy of hepatocellular carcinoma through a possible mechanism involving PI3K/Akt. Mol Cell Biochem 379:191–199Google Scholar
  15. 15.
    Wu F, Li J, Du X et al (2017) Chimeric antibody targeting SRPK-1 in the treatment of non-small cell lung cancer by inhibiting growth, migration and invasion. Mol Med Rep 16:2121–2127Google Scholar
  16. 16.
    Yi N, Xiao M, Jiang F et al (2018) SRPK1 is a poor prognostic indicator and a novel potential therapeutic target for human colorectal cancer. Onco Targets Ther 11:5359–5370Google Scholar
  17. 17.
    Wu Q, Chang Y, Zhang L et al (2013) SRPK1 Dissimilarly Impacts on the Growth, Metastasis, Chemosensitivity and Angiogenesis of Glioma in Normoxic and Hypoxic Conditions. J Cancer 4:727–735Google Scholar
  18. 18.
    Liu H, Hu X, Zhu Y, Jiang G, Chen S (2016) Up-regulation of SRPK1 in non-small cell lung cancer promotes the growth and migration of cancer cells. Tumour Biol 37:7287–7293Google Scholar
  19. 19.
    Koutroumani M, Papadopoulos GE, Vlassi M et al (2017) Evidence for disulfide bonds in SR Protein Kinase 1 (SRPK1) that are required for activity and nuclear localization. PLoS ONE 12:e0171328Google Scholar
  20. 20.
    Ghosh G, Adams JA (2011) Phosphorylation mechanism and structure of serine-arginine protein kinases. FEBS J 278:587–597Google Scholar
  21. 21.
    Zhou Z, Fu XD (2013) Regulation of splicing by SR proteins and SR protein-specific kinases. Chromosoma 122:191–207Google Scholar
  22. 22.
    Nolen B, Yun CY, Wong CF et al (2001) The structure of Sky1p reveals a novel mechanism for constitutive activity. Nat Struct Biol 8:176–183Google Scholar
  23. 23.
    Ding JH, Zhong XY, Hagopian JC et al (2006) Regulated cellular partitioning of SR protein-specific kinases in mammalian cells. Mol Biol Cell 17:876–885Google Scholar
  24. 24.
    Ngo JC, Gullingsrud J, Giang K et al (2007) SR protein kinase 1 is resilient to inactivation. Structure 15:123–133Google Scholar
  25. 25.
    Siebel CW, Feng L, Guthrie C et al (1999) Conservation in budding yeast of a kinase specific for SR splicing factors. Proc Natl Acad Sci USA 96:5440–5445Google Scholar
  26. 26.
    Nikolakaki E, Kohen R, Hartmann AM et al (2001) Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with Scaffold attachment factor-B. J Biol Chem 276:40175–40182Google Scholar
  27. 27.
    Takeuchi M, Yanagida M (1993) A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization. Mol Biol Cell 4:247–260Google Scholar
  28. 28.
    Mermoud JE, Cohen P, Lamond AI (1992) Ser/Thr-specific protein phosphatases are required for both catalytic steps of pre-mRNA splicing. Nucleic Acids Res 20:5263–5269Google Scholar
  29. 29.
    Misteli T, Spector DL (1996) Serine/threonine phosphatise 1 modulates the subnuclear distribution of pre-mRNA splicing factors. Mol Biol Cell 7:1559–1572Google Scholar
  30. 30.
    Mylonis I, Giannakouros T (2003) Protein kinase CK2 phosphorylates and activates the SR protein-specific kinase 1. Biochem Biophys Res Commun 14:650–656Google Scholar
  31. 31.
    Zhong XY, Ding JH, Adams JA et al (2009) Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones. Genes Dev 23:482–495Google Scholar
  32. 32.
    Harper SJ, Bates DO (2008) VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat Rev Cancer 8:880–887Google Scholar
  33. 33.
    Zhong XY, Wang P, Han J et al (2009) SR proteins in vertical integration of gene expression from transcription to RNA processing to translation. Mol Cell 35:1–10Google Scholar
  34. 34.
    Roméria da Silva M, Moreira GA, Gonçalves da Silva RA et al (2015) Splicing regulators and their roles in cancer biology and therapy. Biol Med Res Int 150514:1–12Google Scholar
  35. 35.
    Hertmann AM, Rujescu D, Giannakouros T et al (2001) Regulation of alternative splicing of human tau exon 10 by phosphorylation of splicing factors. Mol Cell Neurosci 18:80–90Google Scholar
  36. 36.
    Andreadis A (2011) Tau splicing and the intricacies of dementia. J Cell Physiol 227:1220–1225Google Scholar
  37. 37.
    Gragoudas ES, Adamis AP, Cunningham ET et al (2004) Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 351:2805–2816Google Scholar
  38. 38.
    Schrijvers BF, Flyvbjerg A, De Vriese AS (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 65:2003–2017Google Scholar
  39. 39.
    Marrelli A, Cipriani P, Liakouli V et al (2011) Angiogenesis in rheumatoid arthritis: a disease specific process or a common response to chronic inflammation? Autoimmun Rev 10:595–598Google Scholar
  40. 40.
    Celletti FL, Hilfiker PR, Ghafouri P et al (2001) Effect of human recombinant vascular endothelial growth factor165 on progression of atherosclerotic plaque. J Am Coll Cardiol 37:2126–2130Google Scholar
  41. 41.
    Jamros MA, Aubol BE, Keshwani MM et al (2015) Intra-domain cross talk regulates serine-arginine protein kinase 1 dependent phosphorylation and splicing function of transformer 2 beta 1. J Biol Chem 290:17269–17281Google Scholar
  42. 42.
    Lemaire R, Prasad J, Kashima T et al (2002) Stability of a PKCI-1-related mRNA is controlled by the splicing factor ASF/SF2: a novel function for SR proteins. Gen Dev 16:594–607Google Scholar
  43. 43.
    Gui JF, Tronchère H, Chandler SD et al (1994) Purification and characterization of a kinase specific for the serine and arginine-rich pre-mRNA splicing factors. Proc Natl Acad Sci USA 91:10824–10828Google Scholar
  44. 44.
    Colwill K, Pawson T, Andrews B et al (1996) The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J 15:265–275Google Scholar
  45. 45.
    Das S, Krainer AR (2014) Emerging functions of SRSF1, splicing factor and oncoprotein, in RNA metabolism and cancer. Mol Cancer Res 12:1195–1204Google Scholar
  46. 46.
    Mavrou A, Brakspear K, Hamdollah-Zadeh M et al (2015) Serine–arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer. Oncogene 34:4311–4319Google Scholar
  47. 47.
    van Roosmalen W, Le Dévédec SE, Golani O et al (2015) Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant. J Clin Invest 125:1648–1664Google Scholar
  48. 48.
    Lin JC, Lin CY, Tarn WY et al (2014) Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events. RNA 20:1621–1631Google Scholar
  49. 49.
    Fu Y, Huang B, Shi Z et al (2013) SRSF1 and SRSF9 RNA binding proteins promote Wnt signalling-mediated tumorigenesis by enhancing beta-catenin biosynthesis. EMBO Mol Med 5:737–750Google Scholar
  50. 50.
    Wilkinson MG, Millar JB (2004) Control of the eukaryotic cell cycle by MAP kinase signaling pathways. FASEB J 14:2147–2157Google Scholar
  51. 51.
    Crowell JA, Steele VE, Fay JR (2007) Targeting the AKT protein kinase for cancer chemoprevention. Mol Cancer Ther 6:2139–2148Google Scholar
  52. 52.
    Feng GS (2012) Conflicting roles of moleucles in hepatocarcinogenesis: paradigm and paradox. Cancer Cell 21:150–154Google Scholar
  53. 53.
    Wang P, Zhou Z, Hu A et al (2014) Both Decreased and Increased SRPK1 Levels Promote Cancer by Interfering with PHLPP-Mediated dephosphorylation of Akt. Mol Cell 54:378–391Google Scholar
  54. 54.
    Adnan M, Patel M, Reddy MN et al (2018) Formulation, evaluation and bioactive potential of Xylaria primorskensis terpenoid nanoparticles from its major compound xylaranic acid. Sci Rep 8:1740Google Scholar
  55. 55.
    Tsuruta F, Masuyama N, Gotoh Y (2002) The phosphatidylinositol 3-kinase (PI3K)-Akt pathway suppresses Bax translocation to mitochondria. J Biol Chem 277:14040–14047Google Scholar
  56. 56.
    Chang Y, Wu Q, Tian T et al (2015) The influence of SRPK1 on glioma apoptosis, metastasis, and angiogenesis through the PI3K/Akt signaling pathway under normoxia. Tumor Biol 3:6083–6093Google Scholar
  57. 57.
    Ren G, Sheng L, Liu H et al (2015) The crucial role of SRPK1 in TGF-b-induced proliferation and apoptosis in the esophageal squamous cell carcinomas. Med Oncol 32:209Google Scholar
  58. 58.
    Adnan M, Khan S, Alshammari E et al (2017) In pursuit of cancer metastasis therapy by bacteria and its biofilms: History or future. Med Hypothesis 100:78–81Google Scholar
  59. 59.
    Fidler I, Kripke M (1980) Tumor cell antigenicity, host immunity, and cancer metastasis. Cancer Immunol Immunother 7:201–205Google Scholar
  60. 60.
    Chambers AF, Groom AC, MacDonald IC (2002) Metastasis:dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572Google Scholar
  61. 61.
    Brodland DG, Zitelli JA (1992) Mechanisms of metastasis. J Am Acad Dermatol 27:1–8Google Scholar
  62. 62.
    Liu H, Hu X, Zhu Y et al (2016) Up-regulation of SRPK1 in non-small cell lung cancer promotes the growth and migration of cancer cells. Tumour Biol 37:7287–7293Google Scholar
  63. 63.
    Qiao M, Li D, Xu T et al (2016) Overexpression of serine-arginine protein kinase 1 and transforming growth factor-β1 were associated with poor prognosis of patients with non-small cell lung cancer. Int J Clin Exp Pathol 9:6857–6866Google Scholar
  64. 64.
    Raithatha SA, Muzik H, Rewcastle NB et al (2000) Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas. Neuro-Oncology 2:145–150Google Scholar
  65. 65.
    Bates DO, Cui TG, Doughty JM (2002) et al VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res 62:4123–4131Google Scholar
  66. 66.
    Amin EM, Oltean S, Hua J et al (2011) WT1 mutants reveal SRPK1 to be a downstream angiogenesis targetby altering VEGF splicing. Cancer Cell 20:768–780Google Scholar
  67. 67.
    Shultz JC, Goehe RW, Wijesinghe DS et al (2010) Alternative splicing of caspase 9 is modulated by thephosphoinositide 3-kinase/Akt pathway via phosphorylation of SRp30a. Cancer Res 70:9185–9196Google Scholar
  68. 68.
    Zhong H, Chiles K, Feldser D et al (2000) Modulation of hypoxia-inducible factor 1alpha expressionby the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications fortumor angiogenesis and therapeutics. Cancer Res 60:1541–1545Google Scholar
  69. 69.
    Jiang BH, Jiang G, Zheng JZ et al (2001) Phosphatidylinositol 3-kinase signaling controls levels of hypoxia inducible factor 1. Cell Growth Differ 12:363–369Google Scholar
  70. 70.
    Birner P, Schindl M, Obermair A et al (2000) Overexpression of hypoxia-inducible factor 1alpha isa marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res 60:4693–4696Google Scholar
  71. 71.
    Giaccia A, Siim BG, Johnson RS (2003) HIF-1 as a target for drug development. Nat Rev Drug Discov 2:803–811Google Scholar
  72. 72.
    Mavrakis KJ, Wendel HG (2008) Translational control and cancer therapy. Cell Cycle 7:2791–2794Google Scholar
  73. 73.
    Harada H, Itasaka S, Kizaka-Kondoh S et al (2009) The Akt/mTOR pathway assures the synthesisof HIF-1alpha protein in a glucose- and reoxygenation-dependentmanner in irradiated tumors. J Biol Chem 284:5332–5342Google Scholar
  74. 74.
    Karni R, De Stanchina E, Lowe SW et al (2007) The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 14:185–193Google Scholar
  75. 75.
    Das S, Anczuk´ow O, Akerman M et al (2012) Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC. Cell Rep 1(2):110–117Google Scholar
  76. 76.
    Maimon A, Mogilevsky M, Shilo A (2014) Mnk2 alternative splicing modulates the p38-MAPK pathway and impacts Ras induced transformation. Cell Rep 7:501–513Google Scholar
  77. 77.
    Adesso L, Calabretta S, Barbagallo F et al Gemcitabine triggers a pro-survival response in pancreatic cancer cells through activation of the MNK2/eIF4E pathway. Oncogene 23:2848–2857Google Scholar
  78. 78.
    Sampath J, Long PR, Shepard RL et al (2003) Human SPF45, a splicing factor, has limited expression in normal tissues, is overexpressed in many tumors, and can confer a multi drug resistant phenotype to cells. Ame J Patho 163:1781–1790Google Scholar
  79. 79.
    Al-Ayoubi AM, Zheng H, Liu Y et al (2012) Mitogen-activated protein kinase phosphorylation of splicingfactor 45 (SPF45) regulates SPF45 alternative splicing site utilization, proliferation, and cell adhesion. Mol Cell Biol 32:2880–2893Google Scholar
  80. 80.
    Peinado H, Moreno-Bueno G, Hardisson D et al (2008) Lysyloxidase-like 2 as a new poor prognosis marker of squamous cell carcinomas. Can Res 68:4541–4550Google Scholar
  81. 81.
    Peng L, Ran YL, Hu H et al (2009) Secreted LOXL2 is a novel therapeutic target that promotes gastric cancer metastasis via the Ssrc/FAK pathway. Carcinogenesis 30:1660–1669Google Scholar
  82. 82.
    Lv GQ, Zou HY, Liao LD et al (2014) Identification of a novel lysyl oxidase-like 2 alternative splicing isoform, LOXL2 Deltae13, in esophageal squamous cellcarcinoma. Biochem Cell Biol 92:379–389Google Scholar
  83. 83.
    Colin C, Voutsinos-Porche B, Nanni I et al (2009) High expression of cathepsin B and plasminogen activator inhibitor type-1 are strong predictors of survival in glioblastomas. ActaNeuropathol 118:745–754Google Scholar
  84. 84.
    Bourboulia D, Jensen-Taubman S, Rittler MR et al (2011) Endogenous angiogenesis inhibitor blocks tumor growth via direct and indirect effects on tumor microenvironment. Am J Pathol 179:2589–2600Google Scholar
  85. 85.
    Yue X, Lan F, Yang W et al (2010) Interruption of beta-catenin suppresses the EGFR pathway by blocking multiple oncogenic targets in human glioma cells. Brain Res 1366:27–37Google Scholar
  86. 86.
    Kim JH, Park DK, Lee CH et al (2012) A new isoflavone glycitein 7-O-beta-D-glucoside 4″-O-methylate, isolated from Cordyceps militaris grown on germinated soybeans extract, inhibits EGF induced mucus hypersecretion in the human lung mucoepidermoid cells. Phytother Res 26:1807–1812Google Scholar
  87. 87.
    Blair KJ, Kiang A, Wang-Rodriguez J et al (2011) EGF and bFGF promote invasion that is modulated by PI3/Akt kinase and Erk in vestibular schwannoma. Otol Neurotol 32:308–314Google Scholar
  88. 88.
    Oda T, Hirota K, Nishi K et al (2006) Activation of hypoxia-inducible factor 1 during macrophage differentiation. Am J Physiol Cell Physiol 291:C104–C113Google Scholar
  89. 89.
    Ben-Hur V, Denichenko P, Siegfried Z et al (2012) S6K1 alternative splicing modulates its oncogenic activity and regulates mTORC1. Cell Rep 3:103–115Google Scholar
  90. 90.
    Yang L, Pang Y, Moses HL (2010) TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol 31:220–227Google Scholar
  91. 91.
    Vagenas K, Spyropoulos C, Gavala V et al (2007) TGFbeta1, TGFbeta2, and TGFbeta3 protein expression in gastric carcinomas: correlation with prognostics factors and patient survival. J Surg Res 139:182–188Google Scholar
  92. 92.
    Liu H, Liu Y, Kong F et al (2015) Elevated levels of SET and MYND domain-containing protein 3 are correlated with overexpression of transforming growth factor-β1 in NSCLC. J Am Coll Surg 221:579–590Google Scholar
  93. 93.
    Ma H, Wei Y, Leng Y et al (2014) TGF-β1-induced expression of Id-1 is associated with tumor progression in NSCLC. Med Oncol 31(7):19Google Scholar
  94. 94.
    Hou YL, Chen H, Dong ZH et al (2013) Clinical significance of serum transforming growth factor-β1 in lung cancer. Cancer Epidemiol 37:750–753Google Scholar
  95. 95.
    Gong L, Song J, Lin X et al (2016) Serine-arginine protein kinase 1 promotes a cancer stem cell-like phenotype through activation of Wnt/β-catenin signalling in NSCLC. J Pathol 240:184–196Google Scholar
  96. 96.
    Hagiwara M, Fukuhara T, Suzuki M et al (2009) Method for controlling protein phosphorilation, and antiviral agents whose active ingredients comprise agents that control SR protein activity. United States Patent US7569536 B2Google Scholar
  97. 97.
    Fukuhara T, Hosoya T, Shimizu S et al (2006) Utilization of host SR protein kinases and RNA-splicing machinery during viral replication. Proc Natl Acad Sci USA 103:11329–11333Google Scholar
  98. 98.
    Siqueira RP, Barbosa Éd AA, Polêto MD et al (2015) Potential anti leukemia effect and structural analyses of SRPK inhibition by N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl) isonicotinamide (SRPIN340). PLoS ONE 10:e0134882Google Scholar
  99. 99.
    Gammons MV, Lucas R, Dean R et al (2014) Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma. Br J Cancer 111:477–485Google Scholar
  100. 100.
    Nowak DG, Amin EM, Rennel ES et al (2010) Regulation of vascular endothelial growth factor (VEGF) splicing from pro-angiogenic to anti-angiogenic isoforms: a novel therapeutic strategy for angiogenesis. J Biol Chem 285:5532–5540Google Scholar
  101. 101.
    Gammons MV, Dick AD, Harper SJ et al (2013) SRPK1 inhibition modulates VEGF splicing to reduce pathological neovascularization in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 54:5797–5806Google Scholar
  102. 102.
    Dong Z, Noda K, Kanda A et al (2013) Specific inhibition of serine/arginine rich protein kinase attenuates choroidal neovascularization. Mol Vis 19:536–543Google Scholar
  103. 103.
    Karakama Y, Sakamoto N, Itsui Y et al (2010) Inhibition of hepatitis C virus replication by a specific inhibitor of serine-arginine-rich protein kinase. Antimicrob Agents Chemother 54:3179–3186Google Scholar
  104. 104.
    Anwar A, Hosoya T, Leong KM et al (2011) The kinase inhibitor SFV785 dislocates dengue virus envelope protein from the replication complex and blocks virus assembly. PLoS ONE 6:e23246Google Scholar
  105. 105.
    Morooka S, Hoshina M, Kii I et al (2015) Identification of a dual inhibitor of SRPK1 and CK2 that attenuates pathological angiogenesis of macular degeneration in mice. Mol Pharmacol 88:316–325Google Scholar
  106. 106.
    Gschwendt M, Kittstein W, Furstenberger G et al (1984) The mouse ear edema: a quantitatively evaluable assay for tumor promoting compounds and for inhibitors of tumor promotion. Can Lett 25:177–185Google Scholar
  107. 107.
    Woo SM, Lee WK, Min KJ et al (2016) Rottlerin induces cyclooxygenase-2 upregulation through an ATF4 and reactive oxygen species-independent pathway in HEI-OC1 cells. Mol Med Rep 14:845–850Google Scholar
  108. 108.
    Yin X, Zhang Y, Su J et al (2016) Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells. Oncotarget 11:66512–66524Google Scholar
  109. 109.
    Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146:873–887Google Scholar
  110. 110.
    Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307Google Scholar
  111. 111.
    Qiu Y, Hoareau-Aveilla C, Oltean S et al (2009) The anti-angiogenic isoforms of VEGF in health and disease. Biochem Soc Trans 37:1207–1213Google Scholar
  112. 112.
    Wang H, Ge W, Jiang W et al (2017) SRPK1siRNA suppresses K562 cell growth and induces apoptosis via the PARPcaspase3 pathway. Mol Med Rep 17:2070–2076Google Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of Biosciences, Bapalal Vaidya Botanical Research CentreVeer Narmad South Gujarat UniversitySuratIndia
  2. 2.Department of Oral Radiology, College of DentistryUniversity of HailHailSaudi Arabia
  3. 3.Department of Biology, Faculty of ScienceUniversity of HailHailSaudi Arabia

Personalised recommendations