Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma

Oncotarget. 2016 Mar 15;7(11):12505-24. doi: 10.18632/oncotarget.7274.

Abstract

HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment.

Keywords: HAX-1; angiogenesis; exosomes; nasopharyngeal carcinoma; prognosis.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis*
  • Animals
  • Carcinoma / blood supply
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Cell Line, Tumor
  • Exosomes / metabolism
  • Female
  • Heterografts
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / blood supply
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Prognosis
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • HAX1 protein, human