Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling

doi:10.1126/sciadv.abq1395

UM > Faculty of Health Sciences > DEPARTMENT OF BIOMEDICAL SCIENCES

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	Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling
	Chen, Si 1,2; Shao, Fangyuan 1,2; Zeng, Jianming 1,2; Guo, Sen 1,2; Wang, Lijian 1,2; Sun, Heng 1,2,3; Lei, Josh Haipeng 1,2; Lyu, Xueying 1,2; Gao, Shuai 4; Chen, Qiang1,2,3 ; Miao, Kai1,2,3 ; Xu, Xiaoling1,2,3 ; Deng, Chu Xia1,2,3
	2023-01-20
Source Publication	Science advances
Volume	9 Issue:3
Abstract	Breast cancer-associated gene 1 (Brca1) deficiency induces the onset of breast cancer formation, accompanied with extensive genetic alterations. Here, we used both the sleeping beauty transposon mutagenesis system and CRISPR-Cas9-mediated genome-wide screening in mice to identify potential genetic alterations that act synergistically with Brca1 deficiency to promote tumorignesis. Both approaches identified Cullin-5 as a tumor suppressor, whose mutation enabled Brca1-deficient cell survival and accelerated tumorigenesis by orchestrating tumor microenvironment. Cullin-5 suppresses cell growth through ubiquitylating and degrading adenosine 3',5'-monophosphate-responsive element binding protein 1 (CREB1), especially under protein damage condition. Meanwhile, Cullin-5 deficiency activated CREB1-CCL2 signaling and resulted in the accumulation of monocytes and polymorphonuclear myeloid-derived suppressor cells, reduction of T cells that benefit tumor progression in both Brca1-deficient cells and wild-type cells. Blocking CREB1 activity either through gene knockout or specific inhibitor treatment suppressed changes in the tumor microenvironment caused by Cullin-5 deficiency and blocked tumor progression.
DOI	10.1126/sciadv.abq1395
URL	View the original
Language	英語English
Scopus ID	2-s2.0-85147046357
Fulltext Access	View Full-Text via DOI View Full-Text via Web of Science View Full-Text via Scopus
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Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES Faculty of Health Sciences
Affiliation	1.Cancer Center, Faculty of Health Sciences, University of Macau, China 2.Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, China 3.MOE Frontiers Science Center for Precision Oncogene, University of Macau, China 4.Key Laboratory of Animal Genetics, Breeding and Reproduction of the MARA, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, China
First Author Affilication	Cancer Centre; Faculty of Health Sciences
Recommended Citation GB/T 7714	Chen, Si,Shao, Fangyuan,Zeng, Jianming,et al. Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling[J]. Science advances, 2023, 9(3).
APA	Chen, Si., Shao, Fangyuan., Zeng, Jianming., Guo, Sen., Wang, Lijian., Sun, Heng., Lei, Josh Haipeng., Lyu, Xueying., Gao, Shuai., Chen, Qiang., Miao, Kai., Xu, Xiaoling., & Deng, Chu Xia (2023). Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling. Science advances, 9(3).
MLA	Chen, Si,et al."Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling".Science advances 9.3(2023).

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