Protein advanced glycation end products (AGEs) formed by non-enzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for AGEs (RAGE), triggering intricate mechanisms that are etiologically related to various chronic diseases, including pancreatic cancer. Many common risk factors of pancreatic cancer are the major sources for the formation of protein AGEs and glycative stress in the human body. Abnormal accumulation of protein AGEs can impair the cellular proteome and promote AGE-RAGE driven proinflammatory signaling cascades, leading to increased oxidative stress, protease resistance, protein dysregulation, transcription activity of STAT, NF-κB and AP-1, aberrant status in ubiquitin-proteasome system and autophagy, as well as other molecular events that are susceptible for the carcinogenic transformation towards the development of neoplasms. Here, we review studies to highlight our understanding in the orchestrated molecular events in bridging the impaired proteome, dysregulated functional networks, and cancer hallmarks initiated upon protein AGE formation and accumulation in pancreatic cancer.

中文翻译：

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蛋白质晚期糖基化终末产物及其对胰腺癌的影响

非酶糖化形成的蛋白质晚期糖基化终末产物（AGE）可以破坏蛋白质的正常结构和功能，并刺激AGEs受体（RAGE），引发与包括胰腺癌在内的多种慢性疾病病因相关的复杂机制。胰腺癌的许多常见危险因素是人体内蛋白质AGEs和糖化应激形成的主要来源。蛋白质 AGE 的异常积累会损害细胞蛋白质组并促进 AGE-RAGE 驱动的促炎信号级联反应，导致氧化应激增加、蛋白酶抵抗、蛋白质失调、STAT、NF-κB 和 AP-1 的转录活性、泛素的异常状态。蛋白酶体系统和自噬，以及其他容易发生致癌转化而发展为肿瘤的分子事件。在这里，我们回顾了一些研究，以强调我们对桥接受损蛋白质组、失调功能网络和胰腺癌中蛋白质 AGE 形成和积累引发的癌症标志的精心策划的分子事件的理解。