27-Hydroxycholesterol promotes metastasis by SULT2A1-dependent alteration in hepatocellular carcinoma.
27-Hydroxycholesterol promotes metastasis by SULT2A1-dependent alteration in hepatocellular carcinoma.
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作者：
氧固醇代谢在多种肿瘤的发生发展中起着重要作用。然而，代谢改变是否能促进肝细胞癌的转移却鲜为人知。在这项研究中，我们发现磺基转移酶家族2A成员1(SULT2A1)到27-羟基胆固醇(27-OHC)的代谢轴在肝癌转移中起关键作用。体内、外27-OHC水平与肝细胞癌的转移密切相关，而与肝细胞癌的增殖无关。此外，SULT2A1在人肝细胞癌组织中的表达显著下调，并与不良预后和肿瘤转移有关。功能获得和功能丧失研究表明，SULT2A1通过调节27-OHC水平抑制肝癌的转移。进一步的机制研究表明，SULT2A1依赖的27-OHC的交替激活了核因子-κB信号通路，通过促进Twist1的表达和上皮-间充质的转变促进了肝癌的转移。综上所述，我们的研究结果提示27-OHC的代谢与肝细胞癌的转移有关。此外，SULT2A1可作为一种潜在的预后生物标志物和预防肝癌转移的治疗靶点。在这项研究中，我们发现磺基转移酶家族2A成员1(SULT2A1)到27-羟基胆固醇(27-OHC)的代谢轴在肝癌转移中起关键作用。此外，SULT2A1可能作为一个潜在的预后生物标志物和预防肝细胞癌转移的治疗靶点。
Oxysterol metabolism plays an important role in the initiation and development of various tumors. However, little is known that the metabolic alternation can promote the metastasis of hepatocellular carcinoma (HCC). In this study, we identify the sulfotransferase family 2A member 1 (SULT2A1) to 27‐hydroxycholesterol (27‐OHC) metabolic axis as playing a critical role in HCC metastasis. The level of 27‐OHC closely corresponded with HCC metastasis instead of proliferation in vitro and in vivo. Also, the expression of SULT2A1 is extremely downregulated in human HCC tissues and is correlated with poor prognosis and tumor metastasis. Gain‐ and loss‐of‐function studies reveal that SULT2A1 suppresses the metastasis of HCC by regulating the level of 27‐OHC. Further mechanistic studies indicated that SULT2A1‐dependent alternation of 27‐OHC activates the nuclear factor‐κB signaling pathway and promotes HCC metastasis by enhancing Twist1 expression and epithelial–mesenchymal transition. In conclusion, our findings indicate the relationship between the metabolism of 27‐OHC and the metastasis of HCC. Moreover, SULT2A1 could act as a potential prognostic biomarker and a therapeutic target for preventing HCC metastasis. In this study, we identify sulfotransferase family 2A member 1 (SULT2A1) to 27‐hydroxycholesterol (27‐OHC) metabolic axis as a critical role in HCC metastasis. Moreover, SULT2A1 may act as a potential prognostic biomarker and a therapeutic target for preventing HCC metastasis.
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DOI：
10.1186/s40880-018-0301-4
发表时间：
2018-05-21
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Cheng C;Geng F;Cheng X;Guo D
通讯作者：
Guo D
影响因子：
--
作者：
DuSell, Carolyn D.;Umetani, Michihisa;McDonnell, Donald P.
通讯作者：
McDonnell, Donald P.
影响因子：
7.7
作者：
Ito A;Hong C;Rong X;Zhu X;Tarling EJ;Hedde PN;Gratton E;Parks J;Tontonoz P
通讯作者：
Tontonoz P
影响因子：
4.5
作者：
Jusakul A;Yongvanit P;Loilome W;Namwat N;Kuver R
通讯作者：
Kuver R
影响因子：
64.8
作者：
Choi, Wan-Su;Lee, Gyuseok;Chun, Jang-Soo
通讯作者：
Chun, Jang-Soo