TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis

Cancer Med. 2019 Dec;8(17):7299-7312. doi: 10.1002/cam4.2582. Epub 2019 Oct 11.

Abstract

The import of proteins into the nucleus plays an important role in tumor development. In addition to the classical nuclear import proteins importin-β and importin-α, there are many nonclassical nuclear import proteins that include TNPO2. The role of TNPO2 as a nonclassical nuclear import protein in tumors is limited. Our previous studies have shown that DYNC1I1 is a poor prognostic factor for gastric cancer and can promote the proliferation and metastasis of gastric cancer cells. An expression profile chip showed that TNPO2 was its potential downstream. DYNC1I1 upregulated TNPO2 expression by upregulating SP1, following which, SP1 recruited and bound to the P300-acetylated TNPO2 promoter region histones, and thus promoted TNPO2 expression. At the same time, TNPO2 promoted gastric cancer cell proliferation and inhibited apoptosis by a mechanism that might be depending on the functional expression of P21.

Keywords: DYNC1I1; P300; SP1; TNPO2; gastric cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Active Transport, Cell Nucleus
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytoplasmic Dyneins / metabolism*
  • E1A-Associated p300 Protein
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Histones / metabolism
  • Humans
  • Promoter Regions, Genetic / genetics
  • Sp1 Transcription Factor / metabolism
  • Stomach Neoplasms / pathology*
  • Up-Regulation
  • beta Karyopherins / genetics
  • beta Karyopherins / metabolism*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • DYNC1I1 protein, human
  • Histones
  • Sp1 Transcription Factor
  • SP1 protein, human
  • TNPO2 protein, human
  • beta Karyopherins
  • E1A-Associated p300 Protein
  • EP300 protein, human
  • Cytoplasmic Dyneins