PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer

Biochem Biophys Res Commun. 2018 Jun 27;501(3):654-660. doi: 10.1016/j.bbrc.2018.05.039. Epub 2018 May 16.

Abstract

Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial-mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes. Moreover, PAFAH1B2 overexpression in PDAC cells was directly mediated by HIF1a. PAFAH1B2 expression in PDAC clinical specimens correlated positively with HIF1a expression. Overall, our results defined PAFAH1B2 as a target gene of HIF1a and a critical driver of PDAC metastatic behaviors.

Keywords: EMT; HIF1a; PAFAH1B2; PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics*
  • Aged
  • Animals
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Up-Regulation

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Microtubule-Associated Proteins
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PAFAH1B2 protein, human