FAT10 promotes the progression of bladder cancer by upregulating HK2 through the EGFR/AKT pathway
FAT10 promotes the progression of bladder cancer by upregulating HK2 through the EGFR/AKT pathway
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FAT10通过EGFR/AKT通路上调HK2促进膀胱癌的进展
DOI：
10.1016/j.yexcr.2020.112401
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发表时间：
2021
影响因子：
3.7
通讯作者：
Jiang Weifan
中科院分区：
文献类型：
--
作者：
Zou Yan;Du Yunyan;Cheng Cheng;Deng Xueqiang;Shi Zimin;Lu Xiongbing;Hu Honglin;Qiu Jun;Jiang Weifan
泛素样蛋白FAT10和己糖激酶蛋白HK2在几个细胞过程中起重要的调节作用。然而，这两种蛋白之间的关系及其在膀胱癌发病机制中的作用尚不清楚。我们发现，膀胱癌组织中FAT10和HK2蛋白水平明显高于正常癌旁组织。此外，在体内和体外，rnai介导的FAT10沉默导致HK2水平降低并抑制膀胱癌的进展。体外实验结果显示HK2对fat10介导的膀胱癌进展至关重要。目前的研究表明，FAT10通过EGFR/AKT通路正向调节HK2，从而促进膀胱癌的进展。根据我们的研究结果，FAT10被认为通过调节EGFR的降解和泛素化来稳定其表达。本研究结果提示，在膀胱癌的发展过程中，FAT10与HK2存在相关性。此外，我们还发现了一个可能参与HK2调控的新途径。这些发现暗示了FAT10、EGFR/AKT和HK2调控回路在膀胱癌进展中的功能障碍。
The ubiquitin-like protein FAT10 and the hexokinase protein HK2 play vital regulatory roles in several cellular processes. However, the relationship between these two proteins and their role in the pathogenesis of bladder cancer are not well understood. Here, we found that FAT10 and HK2 protein levels were markedly higher in bladder cancer tissues than in normal adjacent tissues. In addition, RNAi-mediated silencing of FAT10 led to reduced HK2 levels and suppressed bladder cancer progressionin vivoandin vitro.The results of ourin vivoandin vitroexperiments revealed that HK2 is critical for FAT10-mediated progression of bladder cancer. The current study demonstrated that FAT10 enhanced the progression of bladder cancer by positively regulating HK2 via the EGFR/AKT pathway. Based on our findings, FAT10 is believed to stabilize EGFR expression by modulating its degradation and ubiquitination. The results of the current study indicate that there is a correlation between FAT10 and HK2 in the progression of bladder cancer. In addition, we identified a new pathway that may be involved in the regulation of HK2. These findings implicate dysfunction of the FAT10, EGFR/AKT, and HK2 regulatory circuit in the progression of bladder cancer.