In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 21, No. 5 ( 2017-05), p. 860-870
Abstract:
Natural killer ( NK ) cells play an important role in preventing cancer development. NK group 2 member D ( NKG 2D) is an activating receptor expressed in the membrane of NK cells. Tumour cells expressing NKG 2 DL become susceptible to an immune‐dependent rejection mainly mediated by NK cells. The paradoxical roles of transforming growth factor beta ( TGF ‐β) in regulation of NKG 2 DL are presented in many studies, but the mechanism is unclear. In this study, we showed that TGF ‐β up‐regulated the expression of NKG 2 DL s in both PC 3 and HepG2 cells. The up‐regulation of NKG 2 DL s was characterized by increasing the expression of UL 16‐binding proteins ( ULBP s) 1 and 2. TGF ‐β treatment also increased the expression of transcription factor SP 1. Knockdown of SP 1 significantly attenuated TGF ‐β‐induced up‐regulation of NKG 2 DL s in PC 3 and HepG2 cells, suggesting that SP 1 plays a key role in TGF ‐β‐induced up‐regulation of NKG 2 DL s. TGF ‐β treatment rapidly increased SP 1 protein expression while not mRNA level. It might be due to that TGF ‐β can elevate SP 1 stability by activating PI 3K/ AKT signalling pathway, subsequently inhibiting GSK ‐3β activity and decreasing the association between SP 1 and GSK ‐3β. Knockdown of GSK ‐3β further verified our findings. Taken together, these results revealed that AKT / GSK ‐3β‐mediated stabilization of SP 1 is required for TGF ‐β induced up‐regulation of NKG 2 DL s. Our study provided valuable evidence for exploring the tumour immune modulation function of TGF ‐β.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2017.21.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2076114-4
