Fucosyltransferase 8 regulation and breast cancer suppression by transcription factor activator protein 2γ,Cancer Science

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Fucosyltransferase 8 regulation and breast cancer suppression by transcription factor activator protein 2γ
Cancer Science ( IF 4.5 ) Pub Date : 2021-05-25 , DOI: 10.1111/cas.14987
Minxing Ma ₁ , Dong Guo ₂ , Zengqi Tan ₃ , Jun Du ₁ , Feng Guan ₃ , Xiang Li ₄

Affiliation

Alterations of glycosyltransferase expression are often associated with tumor occurrence and progression. Among the many glycosyltransferases, increased expression of fucosyltransferase 8 (FUT8) has been frequently observed to be involved in progression and metastasis of various types of cancer. The regulatory mechanisms of FUT8 expression remain unclear. FUT8 expression was shown, in this study, to be elevated in breast cancer. Systematic analysis revealed that transcription factor activator protein 2γ (AP-2γ) is the target gene of microRNA-10b (miR-10b), which we previously identified as a positive regulator of FUT8. Overexpression of AP-2γ inhibited FUT8 expression, with associated reduction of cell invasiveness and migration ability. AP-2γ was capable of binding to transcription factor STAT3, and phosphorylation of STAT3 induced transcription of the FUT8 gene. On the basis of our findings, we propose that binding of AP-2γ to STAT3 results in formation of the AP-2γ/STAT3 complex and consequent inhibition of STAT3 phosphorylation, thereby preventing entry of p-STAT3 into the nucleus to initiate FUT8 transcription. This study clarifies the molecular mechanisms whereby transcription factor AP-2γ regulates FUT8 expression in breast cancer.

中文翻译：

岩藻糖基转移酶 8 调节和转录因子激活蛋白 2γ 对乳腺癌的抑制

糖基转移酶表达的改变通常与肿瘤的发生和进展有关。在众多糖基转移酶中，经常观察到岩藻糖基转移酶 8 (FUT8) 表达增加与各种癌症的进展和转移有关。FUT8 表达的调控机制尚不清楚。在这项研究中，FUT8 表达在乳腺癌中升高。系统分析表明，转录因子激活蛋白 2γ (AP-2γ) 是 microRNA-10b (miR-10b) 的靶基因，我们之前将其鉴定为 FUT8 的正调节因子。AP-2γ的过表达抑制了FUT8的表达，并伴随着细胞侵袭性和迁移能力的降低。AP-2γ 能够与转录因子 STAT3 结合，STAT3 的磷酸化诱导 FUT8 基因的转录。根据我们的研究结果，我们提出 AP-2γ 与 STAT3 的结合导致 AP-2γ/STAT3 复合物的形成和随后的 STAT3 磷酸化抑制，从而阻止 p-STAT3 进入细胞核以启动 FUT8 转录。本研究阐明了转录因子 AP-2γ 在乳腺癌中调节 FUT8 表达的分子机制。

更新日期：2021-05-25

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