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Blocking MCT4 SUMOylation inhibits the growth of breast cancer cells
Molecular Carcinogenesis ( IF 3.0 ) Pub Date : 2021-08-04 , DOI: 10.1002/mc.23336
Xiao Hu 1 , Zhanzhao Liu 2 , Xianxian Duan 2 , Xiao Han 1 , Mengci Yuan 2 , Lingyan Liu 3 , Xiaojun Xia 4 , Ning Li 5 , Junfang Qin 2 , Yue Wang 2, 6
Affiliation  

Monocarboxylate transporter 4 (MCT4) is highly expressed in various types of solid neoplasms including breast cancer (BC); however, the pro-tumor functions underlying its increased expression have not been explained. Here, we examined the roles of posttranslational modifications to MCT4 in BC, particularly SUMOylation. Our findings revealed that SUMOylation of MCT4 inhibited its degradation and stabilized MCT4 protein levels, while ubiquitination facilitated MCT4 degradation. The E3 ubiquitin ligases β-TRCP and FBW7 interacted with MCT4 at the DSG-box and TPETS sequences, respectively, and Lys448 (K448) of MCT4 could be modified by SUMO chains. Our key finding was that K448 was crucial for MCT4 SUMOylation. Moreover, mutations of K448 abolished MCT4 expression, delaying the growth of BC. This study suggested that SUMOylation of K448 increased MCT4 levels, and mutations of K448 in MCT4 could have therapeutic significance in BC.

中文翻译:

阻断 MCT4 SUMOylation 抑制乳腺癌细胞的生长

单羧酸转运蛋白 4 (MCT4) 在包括乳腺癌 (BC) 在内的各种实体肿瘤中高度表达;然而,尚未解释其表达增加背后的促肿瘤功能。在这里,我们研究了 BC 中 MCT4 的翻译后修饰的作用,特别是 SUMOylation。我们的研究结果表明,MCT4 的 SUMOylation 抑制了其降解并稳定了 MCT4 蛋白水平,而泛素化促进了 MCT4 降解。E3泛素连接酶β-TRCP 和 FBW7 分别在 DSG-box 和 TPETS 序列处与 MCT4 相互作用,并且 MCT4 的 Lys448 (K448) 可以被 SUMO 链修饰。我们的主要发现是 K448 对 MCT4 SUMOylation 至关重要。此外,K448 的突变消除了 MCT4 的表达,延迟了 BC 的生长。该研究表明 K448 的 SUMOylation 增加了 MCT4 水平,并且 MCT4 中 K448 的突变可能在 BC 中具有治疗意义。
更新日期:2021-09-13
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