Cutting edge: NANOG activates autophagy under hypoxic stress by binding to BNIP3L promoter.

  • Tumor Immunotherapy and Microenvironment
February 15, 2017 By:
  • Hasmim M
  • Janji B
  • Khaled M
  • Noman MZ
  • Louache F
  • Bordereaux D
  • Abderamane A
  • Baud V
  • Mami-Chouaib F
  • Chouaib S.

Hypoxia upregulates the core pluripotency factors NANOG, SOX2, and OCT4, associated with tumor aggressiveness and resistance to conventional anticancer treatments. We have previously reported that hypoxia-induced NANOG contributed in vitro to tumor cell resistance to autologous-specific CTL and in vivo to the in situ recruitment of immune-suppressive cells. In this study, we investigated the mechanisms underlying NANOG-mediated tumor cell resistance to specific lysis under hypoxia. We demonstrated the tumor-promoting effect of hypoxia on tumor initiation into immunodeficient mice using human non-small lung carcinoma cells. We next showed a link between NANOG and autophagy activation under hypoxia because inhibition of NANOG decreased autophagy in tumor cells. Chromatin immunoprecipitation and luciferase reporter assays revealed a direct binding of NANOG to a transcriptionally active site in a BNIP3L enhancer sequence. These data establish a new link between the pluripotency factor NANOG and autophagy involved in resistance to CTL under hypoxia.

2017 Feb. J Immunol.198(4):1423-1428. Epub 2017 Jan 16.
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