Overexpressed targeting protein for Xklp2 (TPX2) serves as a promising prognostic marker and therapeutic target for gastric cancer

Cancer Biol Ther. 2016 Aug 2;17(8):824-32. doi: 10.1080/15384047.2016.1195046. Epub 2016 Jun 17.

Abstract

The targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a putative oncogene in different human cancers. This study assessed TPX2 expression in gastric cancer tissue samples and then determined the effects of TPX2 knockdown on the regulation of gastric cancer cell malignant behaviors in vitro. Tissue samples from 115 gastric cancer patients were analyzed for TPX2 expression. The effects of TPX2 siRNA on gastric cancer cells were assessed in vitro, including cell viability, cell cycle distribution, apoptosis, migration, and invasion. The data showed that TPX2 was overexpressed in gastric cancer tissues compared to that in the adjacent normal epithelia. Moreover, TPX2 overexpression was associated with a poor overall survival and was an independent prognostic predictor of gastric cancer. In addition, the in vitro study further confirmed the ex vivo data, i.e., knockdown of TPX2 expression reduced gastric cancer cell viability but induced apoptosis and arrested cells at the G2/M phase of the cell cycle. Knockdown of TPX2 expression also inhibited the tumor cell migration and invasion capacity in vitro. At the gene level, knockdown of TPX2 expression upregulated the levels of cyclin B1, cdk4, p53, Bax, caspase-3, and E-cadherin, but downregulated the levels of cyclin D1, cdk2, N-cadherin, slug, matrix metalloprotease (MMP)-2, and MMP-9, suggesting that knockdown of TPX2 expression suppressed tumor cell epithelial-mesenchymal transition (EMT). This study demonstrated that detection of TPX2 overexpression could serve as a prognostic marker and therapeutic target for gastric cancer.

Keywords: Apoptosis; EMT; TPX2; cell cycle arrest; drug target; gastric cancer; prognostic marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / genetics
  • Cell Growth Processes / genetics
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Profiling / methods
  • Gene Knockdown Techniques
  • Humans
  • Microtubule-Associated Proteins / biosynthesis*
  • Microtubule-Associated Proteins / genetics
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transfection

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • TPX2 protein, human