CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling

UM > Faculty of Health Sciences > DEPARTMENT OF BIOMEDICAL SCIENCES

Status	已發表Published
	CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling
	Zhao, ZQ; Hao, DP; Wang, L.; LI, JJ; MENG, Y; LI, PP; WANG, Y; ZHANG, C; ZHOU, HS; GARDNER, K; Di, L.
	2018-11-15
Source Publication	Oncogene
ISSN	0950-9232
Pages	1-16
Abstract	Metastasis is the process through which the primary cancer cells spread beyond the primary tumor and disseminate to other organs. Most cancer patients die of metastatic disease. EMT is proposed to be the initial event associated with cancer metastasis and how it occurred is still a mystery. CtBP is known as a co-repressor abundantly expressed in many types of cancer and regulates genes involved in cancer initiation, progression, and metastasis. We found that CtBP regulates intracellular cholesterol homeostasis in breast cancer cells by forming a complex with ZEB1 and transcriptionally repressing SREBF2 expression. Importantly, CtBP repression of intracellular cholesterol abundance leads to increased EMT and cell migration. The reason is that cholesterol negatively regulates the stability of TGF-β receptors on the cell membrane. Interestingly, TGF-β is also capable of reducing intracellular cholesterol relying on the increased recruitment of ZEB1 and CtBP complex to SREBF2 promoter. Thus, we propose a feedback loop formed by CtBP, cholesterol, and TGF-β signaling pathway, through which TGF-β triggers the cascade that mobilizes the cancer cells for metastasis. Consistently, the intravenous injection of breast cancer cells with ectopically CtBP expression show increased lung metastasis depending on the reduction of intracellular cholesterol. Finally, we analyzed the public breast cancer datasets and found that CtBP expression negatively correlates with SREBF2 and HMGCR expressions. High expression of CtBP and low expression of SREBF2 and HMGCR significantly correlates with high EMT of the primary tumors.
Keyword	CtBP Cholesterol Metastasis
Language	英語English
The Source to Article	PB_Publication
PUB ID	42425
Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	Di, L.
Recommended Citation GB/T 7714	Zhao, ZQ,Hao, DP,Wang, L.,et al. CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling[J]. Oncogene, 2018, 1-16.
APA	Zhao, ZQ., Hao, DP., Wang, L.., LI, JJ., MENG, Y., LI, PP., WANG, Y., ZHANG, C., ZHOU, HS., GARDNER, K., & Di, L. (2018). CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling. Oncogene, 1-16.
MLA	Zhao, ZQ,et al."CtBP promotes metastasis of breast cancer through repressing cholesterol and activating TGF-β signaling".Oncogene (2018):1-16.

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