Hepatocyte-generated 27-hydroxycholesterol promotes the growth of melanoma by activation of estrogen receptor alpha
Hepatocyte-generated 27-hydroxycholesterol promotes the growth of melanoma by activation of estrogen receptor alpha
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肝细胞产生的27-羟基胆固醇通过激活雌激素受体α促进黑色素瘤的生长
DOI：
10.1002/jcb.26498
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Tian W;Pang W;Ge Y;He X;Wang D;Li X;Hou H;Zhou D;Feng S;Chen Z;Yang Y
Cholesterol plays an important role in maintaining normal physiological function of human body. However, excessive intake will induce a series of diseases including cancer. For melanoma, the relationship between hypercholesterolemia and its incidence remains unknown. The cholesterol metabolite 27‐hydroxy cholesterol (27‐HC) catalyzed by CYP27A1 has been reported to activate estrogen receptor (ER). As studies have indicated that melanoma expresses ER, we designed experiments to explore whether 27‐HC could link hypercholesterolemia and melanoma. In this study, hepatocyte‐specific CYP27A1−/−mice were generated by CRISPR/Cas9 technology. The results revealed that high‐cholesterol diet induced metabolism disorder and promoted the melanoma growth through 27‐HC. Further study found that 27‐HC promoted the growth of melanoma cells by activating ERα and eliciting the AKT and MAPK signaling pathway. This study puts forward the important role of 27‐HC in the development of melanoma for the first time, links hypercholesterolemia with melanoma progression. The research also provides the rationale for the use of tamoxifen in melanoma therapy. The levels of 27‐HC in blood could act as a novel biomarker for tamoxifen treatment in melanoma patients.
