Department of General Surgery & Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy-Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Int J Mol Sci. 2024 Aug 23;25(17):9138. doi: 10.3390/ijms25179138.
Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the genes have been identified in humans, i.e., AP-2α/β/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2β and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.
激活增强子结合蛋白 2（AP-2）是一类转录因子（TFs），在调控胚胎和致癌发育中发挥着关键作用。除了剪接异构体外，人类还鉴定出由 基因编码的五个主要家族成员，即 AP-2α/β/γ/δ/ε。一般来说，前三个 TF 比 AP-2δ或 AP-2ε研究得更透彻。目前，关于胃肠病学研究中 AP-2 家族的文献相对较少，缺乏对现有知识的全面概述和进一步研究方向的建议。在此，我们收集了 AP-2 TF 的可用胃肠病学数据，讨论了每个家族成员的最新医学应用，并提出了潜在的未来方向。在胃肠道肿瘤中，对 AP-2 的研究主要集中在两个描述最详细的家族成员，AP-2α 和 AP-2γ。令人惊讶的是，过去十年的研究强调了 AP-2ε 在胃癌（GC）和结直肠癌（CRC）耐药中的重要性。尽管关于胃肠疾病的许多问题仍有待阐明，但现有数据无疑为抗癌靶向治疗和克服化疗耐药性开辟了途径。除了胃肠道癌症外，AP-2 家族成员（主要是 AP-2β 和少量的 AP-2γ）还与其他健康问题有关，如肥胖、2 型糖尿病、肝功能障碍和假性肠梗阻。另一方面，AP-2δ 在胃肠病学疾病中的研究甚少，需要进一步研究以阐明其作用。总之，尽管 AP-2 在胃肠病学研究中受到的关注有限，但这些转录因子的关键功能已经开始显现，未来需要进一步探索。
