title: The crucial role of SRPK1 in TGF-β-induced proliferation and apoptosis in the esophageal squamous cell carcinomas.
abstract: In recent years, transforming growth factor-β (TGF-β) and the serine-arginine protein kinase 1 (SRPK1) have been recommended as a key signal mediator that is involved in oncogenesis. However, the mechanisms underlying TGF-β-SRPK1 pathway-mediated proliferation and apoptosis in the esophageal squamous cell carcinomas (ESCC) have not been well featured till now. We used immunohistochemistry, immunoblotting, and RT-PCR to assess the expression of SRPK1 in 120 cases of ESCC samples and cell lines. Subsequently, some in vitro assays were also applied where cells were administrated with TGF-β. We found that SRPK1 was highly expressed in ESCC tissues and acts as an independent prognostic factor for ESCC patients. In vitro studies indicated that overexpression of wild-type SRPK1 promoted ESCC cell proliferation, while overexpression of the kinase-dead mutant of SRPK1 or RNA interference against SRPK1 suppressed cell growth and enhanced apoptosis. The knockdown of SRPK1 also inhibited subcutaneous xenografts' growth of ESCC cells in nude mice. Furthermore, Western bolt analysis showed SRPK1 can activate Akt phosphorylation and inhibit JNK phosphorylation. In conclusion, SRPK1 mediates TGF-β-induced proliferation and apoptosis by regulating AKT and JNK in ESCC, which indicates TGF-β-SRPK1 pathway may be suggested as a useful target to affect the progression of ESCC.
authors.affiliation: Department of Oncology, Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan, 250014, People's Republic of China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Ren
authors.forename: Lijun
authors.initials: L
authors.lastname: Sheng
authors.forename: Haibo
authors.initials: H
authors.lastname: Liu
authors.forename: Yahong
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuji
authors.initials: Y
authors.lastname: An
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010766:Phosphorylation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D016212:Transforming Growth Factor beta; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt