葡萄糖失调与癌症发展密切相关，癌症在2型糖尿病（T2D）患者中普遍存在。我们旨在阐明葡萄糖失调对人膀胱癌（BC）自噬机制的影响。本回顾性研究纳入了220例BC患者。通过免疫组织化学、免疫印迹和定量实时PCR（qPCR）分析了YAP1、TAZ和AMPK、EMT相关标记物以及自噬标记蛋白的表达。此外，还将T24和UMUC-3 BC细胞培养在含有不同葡萄糖浓度的培养基中，通过免疫印迹和qPCR分析了YAP1、TAZ、AMPK和EMT相关标记物以及自噬标记蛋白的表达。通过免疫荧光和电子显微镜观察到了自噬现象。使用糖尿病的裸鼠模型评估肿瘤的生长、转移和生存情况。与仅患BC的患者相比，同时患T2D的BC患者显示更差的病理分级和肿瘤-淋巴结-转移分期。T2D患者的BC样本中YAP1和TAZ的表达上调。从机制上讲，高葡萄糖（HG）促进了BC的体外和体内进展，并抑制了自噬。具体地，在HG条件下，各种自噬标记蛋白和AMPK呈负调节，与YAP1和TAZ的表达相关。这些结果表明HG抑制了BC中的自噬并促进了癌症的发展。YAP1/TAZ/AMPK信号传导在调节自噬的葡萄糖失调过程中起关键作用。靶向这些作用器具有治疗意义，并可用作T2D患者BC的预后标记物。©2023作者。《细胞与分子医学杂志》由细胞与分子医学和John Wiley＆Sons Ltd.出版。

Glucose dysregulation is strongly correlated with cancer development, and cancer is prevalent in patients with Type 2 diabetes (T2D). We aimed to elucidate the mechanism underlying autophagy in response to glucose dysregulation in human bladder cancer (BC). 220 BC patients were included in this retrospective study. The expression of YAP1, TAZ and AMPK, EMT-associated markers, and autophagy marker proteins was analysed by immunohistochemistry, western blotting, and quantitative real-time PCR (qPCR). Further, T24 and UMUC-3 BC cells were cultured in media with different glucose concentrations, and the expression of YAP1, TAZ, AMPK and EMT-associated markers, and autophagy marker proteins was analysed by western blotting and qPCR. Autophagy was observed by immunofluorescence and electron microscopy. BC cell viability was tested using MTT assays. A xenograft nude mouse model of diabetes was used to evaluate tumour growth, metastasis and survival. A poorer pathologic grade and tumour-node-metastasis stage were observed in patients with BC with comorbid T2D than in others with BC. YAP1 and TAZ were upregulated in BC samples from patients with T2D. Mechanistically, high glucose (HG) promoted BC progression both in vitro and in vivo and inhibited autophagy. Specifically, various autophagy marker proteins and AMPK were negatively regulated under HG conditions and correlated with YAP1 and TAZ expression. These results demonstrate that HG inhibits autophagy and promotes cancer development in BC. YAP1/TAZ/AMPK signalling plays a crucial role in regulating glucose dysregulation during autophagy. Targeting these effectors exhibits therapeutic significance and can serve as prognostic markers in BC patients with T2D.© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.