Alternative NF-kappa B signaling promotes colorectal tumorigenesis through transcriptionally upregulating Bcl-3

doi:10.1038/s41388-018-0363-4

	Alternative NF-kappa B signaling promotes colorectal tumorigenesis through transcriptionally upregulating Bcl-3
	Tao, Yu 1,2; Liu, Zhanjie 1,2; Hou, Yingyong 3; Wang, Shouli 4; Liu, Sanhong1,2,5 ; Jiang, Yuhang 1,2; Tan, Dan 6; Ge, Qiulin 7; Li, Cuifeng 1,2; Hu, Yiming 1,2; Liu, Zhi 1,2; Chen, Xi 1,2; Wang, Qi 1,2; Wang, Mingliang 6; Zhang, Xiaoren 1,2,8
	2018-11
发表期刊	ONCOGENE (IF:6.9[JCR-2023],7.5[5-Year])
ISSN	0950-9232
卷号	37 期号:44 页码:5887-5900
发表状态	已发表
DOI	10.1038/s41388-018-0363-4
摘要	Multiple studies have shown that chronic inflammation is closely related to the occurrence and development of colorectal cancer (CRC). Classical NF-kappa B signaling, the key factor in controlling inflammation, has been found to be of great importance to CRC development. However, the role of alternative NF-kappa B signaling in CRC is still elusive. Here, we found aberrant constitutive activation of alternative NF-kappa B signaling both in CRC tissue and CRC cells. Knockdown of RelB downregulates c-Myc and upregulates p27(Kip1) protein level, which inhibits CRC cell proliferation and retards CRC xenograft growth. Conversely, overexpression of RelB increases proliferation of CRC cells. In addition, we revealed a significant correlation between Bcl-3 and RelB in CRC tissues. The expression of RelB was consistent with the expression of Bcl-3 and the phosphorylation of Bcl-3 downstream proteins p-Akt (S473) and p-GSK3 beta (S9). Bcl-3 overexpression can restore the phenotype changes caused by RelB knockdown. Importantly, we demonstrated that alternative NF-kappa B transcriptional factor (p52:RelB) can directly bind to the promoter region of Bcl-3 gene and upregulate its transcription. Moreover, the expression of RelB, NF-kappa B2 p52, and Bcl-3 was associated with poor survival of CRC patients. Taken together, these results represent that alternative NF-kappa B signaling may function as an oncogenic driver in CRC, and also provide new ideas and research directions for the pathogenesis, prevention, and treatment of other inflammatory-related diseases.
收录类别	SCI ; SCIE
语种	英语
资助项目	Natural Science Foundation of Shanghai[14ZR1426300] ; Natural Science Foundation of Shanghai[18ZR1424400] ; Natural Science Foundation of Shanghai[18ZR1446400]
WOS研究方向	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS类目	Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS记录号	WOS:000448943100006
出版者	NATURE PUBLISHING GROUP
WOS关键词	FAMILY-MEMBER BCL-3 ; C-MYC ; CANCER STATISTICS ; PROSTATE-CANCER ; ACTIVATION ; INFLAMMATION ; ANGIOGENESIS ; EXPRESSION ; BINDING ; KINASE
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/28303
专题	免疫化学研究所_特聘教授组_干细胞生物学实验室
通讯作者	Wang, Mingliang; Zhang, Xiaoren
作者单位	1.Shanghai Jiao Tong Univ, Inst Hlth Sci, Key Lab Stem Cell Biol, Sch Med, Shanghai 200025, Peoples R China 2.Chinese Acad Sci, SIBS, Shanghai 200025, Peoples R China 3.Fudan Univ, Zhongshan Hosp, Dept Pathol, 180 Fenglin Rd, Shanghai 200032, Peoples R China 4.Soochow Univ, Dept Pathol, Sch Med, Suzhou 215123, Peoples R China 5.Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 6.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Gen Surg, Shanghai 200025, Peoples R China 7.Shanghai Jiao Tong Univ, Peoples Hosp 6, Dept Obstet & Gynecol, Shanghai, Peoples R China 8.Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou 510000, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Tao, Yu,Liu, Zhanjie,Hou, Yingyong,et al. Alternative NF-kappa B signaling promotes colorectal tumorigenesis through transcriptionally upregulating Bcl-3[J]. ONCOGENE,2018,37(44):5887-5900.
APA	Tao, Yu.,Liu, Zhanjie.,Hou, Yingyong.,Wang, Shouli.,Liu, Sanhong.,...&Zhang, Xiaoren.(2018).Alternative NF-kappa B signaling promotes colorectal tumorigenesis through transcriptionally upregulating Bcl-3.ONCOGENE,37(44),5887-5900.
MLA	Tao, Yu,et al."Alternative NF-kappa B signaling promotes colorectal tumorigenesis through transcriptionally upregulating Bcl-3".ONCOGENE 37.44(2018):5887-5900.