title: Serine-arginine protein kinase 1 promotes a cancer stem cell-like phenotype through activation of Wnt/β-catenin signalling in NSCLC.
abstract: Cancer stem cells (CSCs) are commonly associated with cancer recurrence and metastasis that occurs in up to 30-55% of non-small-cell lung carcinoma (NSCLC) patients. Herein, we showed that serine-arginine protein kinase 1 (SRPK1) was highly expressed at both the mRNA and the protein levels in human NCSLC. SRPK1 was associated with the clinical features of human NSCLC, including clinical stage (p < 0.001) and T (p = 0.001), N (p = 0.007), and M (p = 0.001) classifications. Ectopic overexpression of SRPK1 promoted the acquisition of a stem cell-like phenotype in human NSCLC cell lines cultured in vitro. Overexpression of SRPK1 increased sphere formation and the proportion of side-population cells that exclude Hoechst dye. Conversely, SRPK1 silencing reduced the number of spheres and the proportion of side-population cells. Mouse studies indicated that SRPK1 promoted NSCLC cell line tumour growth and SRPK1 overexpression reduced the number of tumour cells required to initiate tumourigenesis in vivo. Mechanistically, gene set enrichment analysis showed that Wnt/β-catenin signalling correlated with SRPK1 mRNA levels and this signalling pathway was hyperactivated by ectopic SRPK1 expression in NSCLC cell lines. Immunofluorescence demonstrated that SRPK1 enhanced β-catenin accumulation in the nuclei of NSCLC cell lines, and inhibition of β-catenin signalling abrogated the SRPK1-induced stem cell-like phenotype. Together, our findings suggest that SRPK1 promotes a stem cell-like phenotype in NSCLC via Wnt/β-catenin signalling. Moreover, SRPK1 may represent a novel target for human NSCLC diagnosis and therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Key Laboratory of Translational Medicine of Tumor, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Gong
authors.affiliation: Key Laboratory of Translational Medicine of Tumor, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, China.|State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China.|Department of Biochemistry, Sun Yat-sen University, Guangzhou, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Key Laboratory of Translational Medicine of Tumor, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, China.
authors.forename: Fakai
authors.initials: F
authors.lastname: Wei
authors.affiliation: Key Laboratory of Translational Medicine of Tumor, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Translational Medicine of Tumor, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, China.
authors.forename: Zimei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.affiliation: Key Laboratory of Translational Medicine of Tumor, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Translational Medicine of Tumor, Department of Biochemistry and Molecular Biology, Health Science Center, Shenzhen University, Shenzhen, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liang
authors.affiliation: The Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: XiaoYuan
authors.initials: X
authors.lastname: Fu
authors.affiliation: The Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Junqiang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pathology, College of Health Science, Guangzhou Medical University, Guangzhou, Guangdong, China. 2314970312@qq.com.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China. songlb@sysucc.org.cn.
authors.forename: Libing
authors.initials: L
authors.lastname: Song
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: NSCLC; SRPK1; Wnt/β-catenin signalling; stem cell-like phenotype