mTOR up-regulation of BEX4 promotes lung adenocarcinoma cell proliferation by potentiating OCT4

Biochem Biophys Res Commun. 2018 Jun 2;500(2):302-309. doi: 10.1016/j.bbrc.2018.04.064. Epub 2018 Apr 19.

Abstract

Previously, BEX family members have been reported to participate in cancer development. However, little is known about the role of BEX4 in lung adenocarcinoma (LAC). Here, we found that BEX4 was over-expressed in LAC tissues compared with adjacent tissues. LAC tissues from metastatic patients exhibited higher expression of BEX4 comparing to those from non-metastatic ones. In vitro, BEX4 ectopic expression accelerated the proliferation of both A549 and H1975 cells. By contrast, knockdown of BEX4 suppressed the proliferation of A549 and H1975 cells. BEX4 positively regulated the expression of OCT4, silencing of which reduced the proliferation of A549 and H1975 cells with over-expressed BEX4. Additionally, mTOR activation, which is frequently observed in LAC, potentiated BEX4 depending on mTORC1 but not mTORC2. BEX4 abundance dictated the sensitivity of A549 and H1975 cells to rapamycin treatment. Our findings reveal that BEX4 is an oncogene in LAC and may contribute to the hyper-active mTOR-induced LAC development.

Keywords: BEX4; Lung adenocarcinoma; OCT4; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Octamer Transcription Factor-3 / metabolism*
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation / genetics*

Substances

  • BEX4 protein, human
  • Microtubule-Associated Proteins
  • Octamer Transcription Factor-3
  • Oncogene Proteins
  • POU5F1 protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases