Up-regulation of SRPK1 in non-small cell lung cancer promotes the growth and migration of cancer cells

Tumour Biol. 2016 Jun;37(6):7287-93. doi: 10.1007/s13277-015-4510-z. Epub 2015 Dec 14.

Abstract

Dys-regulation of serine-arginine protein kinase 1 (SRPK1) has been reported in non-small cell lung cancer (NSCLC). However, its functions in the progression of NSCLC remain poorly understood. In this study, the expression of SRPK1 in NSCLC tissues was determined using real-time PCR, and the roles of SRPK1 in the progression of NSCLC were investigated. It was found that both the mRNA level and the protein level of SRPK1 were up-regulated in NSCLC tissues. Forced expression of SRPK1 promoted the growth and migration of NSCLC cells, while knocking down the expression of SRPK1 inhibited the growth, migration, and tumorigenicity of NSCLC cells. Mechanism studies showed that SRPK1 activated the transcriptional activity of beta-catenin/T-cell factor (TCF) complex, and knocking down the expression of SRPK1 attenuated the expression of target genes of beta-catenin/T-cell factor (TCF) complex. In addition, silencing the expression of SRPK1 down-regulated the phosphorylation of GSK3beta. Taken together, SRPK1 might play an oncogenic role in NSCLC, and SRPK1 might be a therapeutic target for NSCLC.

Keywords: Beta-catenin/TCF signaling; Cell growth and migration; NSCLC; SRPK1.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Enzyme Induction
  • Epithelial Cells
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Heterografts
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Mice, Nude
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology*
  • RNA Interference
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • TCF Transcription Factors / physiology
  • Tumor Stem Cell Assay
  • Up-Regulation
  • beta Catenin / physiology

Substances

  • CTNNB1 protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • TCF Transcription Factors
  • beta Catenin
  • SRPK1 protein, human
  • Glycogen Synthase Kinase 3 beta
  • Protein Serine-Threonine Kinases