Corticotropin-releasing factor induces immune escape of cervical cancer cells by downregulation of NKG2D

Hyunkeun Song, Hyunjin Park, Gabin Park, Yeong Seok Kim, Hyun Kyung Lee, Dong Hoon Jin, Hyung Sik Kang, Dae H.O. Cho, Daeyoung Hur

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Corticotropin-releasing factor (CRF), a coordinator of the body's responses to stress, is found in various cancer tissues and cell lines. However, the exact abilities of CRF to manipulate natural killer (NK) cells during immune response have not been studied. NKG2D is an activating receptor that is expressed on most NK and CD8+ T cells. MHC class I-related chain A (MICA) and UL16-binding protein (ULBP) 1, 2 and 3 are well-known ligands for NKG2D. In the present study, we reported our findings regarding the role of CRF in cervical cancer cell survival. Human cervical cancer cell line, HeLa cells, had significantly higher intracellular expression of UL16-binding protein 2 (ULBP2) following CRF treatment but had only slightly increased surface expression of ULBP2. Notably, MMPi (pan-metalloproteases inhibitor) blocked the release of ULBP2 molecules from the surface of HeLa cells. Furthermore, incubating NK cells with culture supernatants from CRF-treated HeLa cells, which contained soluble NKG2D ligand, reduced NK cell activity by decreasing surface expression of NKG2D. Collectively, downregulation of NKG2D by CRF-induced soluble NKG2D ligand provides a potential mechanism by which cervical cancer cells escape NKG2D-mediated attack under stress conditions.

Original languageEnglish
Pages (from-to)425-430
Number of pages6
JournalOncology reports
Issue number1
Publication statusPublished - 2014 Jul
Externally publishedYes


  • Corticotropin-releasing factor
  • Immune escape
  • NKG2D ligand
  • Natural killer cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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