TY - JOUR
T1 - REGγ deficiency suppresses tumor progression via stabilizing CK1ϵ in renal cell carcinoma article
AU - Chen, Shaojun
AU - Wang, Qingwei
AU - Wang, Longsheng
AU - Chen, Hui
AU - Gao, Xiao
AU - Gong, Dongkui
AU - Ma, Junjie
AU - Kubra, Syeda
AU - Yao, Xudong
AU - Li, Xiaotao
AU - Li, Lei
AU - Zhai, Wei
AU - Zheng, Junhua
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Renal cell carcinoma (RCC) is the most common malignant disease of kidney in adults. The proteasome activator REGγ was previously reported to promote the degradation of multiple important regulatory proteins and involved in the progression and development of numerous human cancers. Here, we first reported that REGγ was upregulated in RCC and its upregulation was correlated with a poor prognosis in RCC patients. REGγ depletion obviously suppressed RCC cells proliferation in vitro and in vivo. Notably, casein kinase 1ϵ (CK1ϵ) was identified as a novel target of REGγ and knockdown of CK1ϵ effectively abolished the effect of REGγ depletion on RCC cells growth. Importantly, we also observed that REGγ depletion activated Hippo signaling pathway via stabilizing CK1ϵ in RCC, indicating the cross-Talk between REGγ/CK1ϵ axis and Hippo pathway during RCC development. In conclusion, our findings suggested that REGγ played a pivotal role in the development of RCC and maybe helpful to identify new therapeutic strategies in the treatment of RCC.
AB - Renal cell carcinoma (RCC) is the most common malignant disease of kidney in adults. The proteasome activator REGγ was previously reported to promote the degradation of multiple important regulatory proteins and involved in the progression and development of numerous human cancers. Here, we first reported that REGγ was upregulated in RCC and its upregulation was correlated with a poor prognosis in RCC patients. REGγ depletion obviously suppressed RCC cells proliferation in vitro and in vivo. Notably, casein kinase 1ϵ (CK1ϵ) was identified as a novel target of REGγ and knockdown of CK1ϵ effectively abolished the effect of REGγ depletion on RCC cells growth. Importantly, we also observed that REGγ depletion activated Hippo signaling pathway via stabilizing CK1ϵ in RCC, indicating the cross-Talk between REGγ/CK1ϵ axis and Hippo pathway during RCC development. In conclusion, our findings suggested that REGγ played a pivotal role in the development of RCC and maybe helpful to identify new therapeutic strategies in the treatment of RCC.
UR - https://www.scopus.com/pages/publications/85047625929
U2 - 10.1038/s41419-018-0646-2
DO - 10.1038/s41419-018-0646-2
M3 - 文章
C2 - 29795381
AN - SCOPUS:85047625929
SN - 2041-4889
VL - 9
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 6
M1 - 627
ER -
