Xian Qingying, Zhu Danxia
Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
J Oncol. 2022 Apr 5;2022:5871188. doi: 10.1155/2022/5871188. eCollection 2022.
Esophageal cancer is one of the most common malignant tumors in the world, which is characterized by high incidence, strong invasiveness, high mortality, and poor prognosis. At present, the therapies include surgery, endoscopic resection, radiotherapy and chemotherapy, targeted therapy, and immunotherapy. The five-year survival rate of esophageal cancer has not been significantly improved, although the medical level has been continuously improved and the management and application of different therapies have been improved day by day. At present, an abnormal gene expression is still regarded as an important factor in the occurrence and development of esophageal cancer. WD repeat and HMG-box DNA binding protein 1(), as a key gene, plays an important role in the occurrence of esophageal cancer. It is known that the protein encoded by is the downstream target of the PI3K/AKT pathway. When PI3Ks is activated by extracellular signals, PI(4,5)P2 on the inner side of the plasma membrane will be converted into PI(3,4,5)P3. Then, PI(3,4,5)P3 can be converted into PI(3,4)P2,PI(4)P and PI(3)P by dephosphorylation of some regulatory factors. PI(3,4,5)P3 recruited AKT to the plasma membrane and combined with its pH domain, resulting in conformational change of AKT. Subsequently, AKT was completely activated by PDK1 and PDK2 and begins to move to the cytoplasm and nucleus. In this process, AKT continuously phosphorylates downstream substrates. WDHD1, as a downstream target of AKT, is also phosphorylated and induces DNA replication. Besides the abnormal regulation of cells by other downstream targets of AKT, it also becomes a potential pathway that may eventually lead to the occurrence of esophageal cancer.
食管癌是世界上最常见的恶性肿瘤之一，具有发病率高、侵袭性强、死亡率高和预后差的特点。目前，治疗方法包括手术、内镜切除、放疗和化疗、靶向治疗及免疫治疗。尽管医疗水平不断提高，不同治疗方法的管理和应用也日益完善，但食管癌的五年生存率仍未得到显著提高。目前，基因表达异常仍被视为食管癌发生发展的重要因素。WD重复和HMG盒DNA结合蛋白1（WDHD1）作为关键基因，在食管癌的发生中起重要作用。已知WDHD1编码的蛋白质是PI3K/AKT信号通路的下游靶点。当PI3Ks被细胞外信号激活时，质膜内侧的PI(4,5)P2会转化为PI(3,4,5)P3。然后，PI(3,4,5)P3可通过一些调节因子的去磷酸化作用转化为PI(3,4)P2、PI(4)P和PI(3)P。PI(3,4,5)P3将AKT招募到质膜并与其pH结构域结合，导致AKT构象改变。随后，AKT被PDK1和PDK2完全激活并开始转移至细胞质和细胞核。在此过程中，AKT持续磷酸化下游底物。WDHD1作为AKT的下游靶点，也会被磷酸化并诱导DNA复制。除了AKT的其他下游靶点对细胞的异常调节外，它也成为一条最终可能导致食管癌发生的潜在途径。
