Department of Medical Oncology, Hyogo Cancer Center, Hyogo, Japan
Anticancer Res. 2024 Oct;44(10):4147-4153. doi: 10.21873/anticanres.17245.
Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor arising from vascular endothelial cells. This study delves into the molecular mechanisms underlying EHE, with a specific focus on the Hippo-YAP/TAZ pathway. EHE is characterized molecularly by transcriptional co-activator with a PDZ-motif (TAZ)-calmodulin binding transcription activator 1 (CAMTA1) or Yes-associated protein (YAP)-transcription factor E3 (TFE3) fusions. YAP/TAZ, a transcription co-activator, binds to transcription factors and regulates gene expression. The YAP/TAZ and its upstream Hippo pathway are involved in cell proliferation and cell contact inhibition, regulating organ size and carcinogenesis. In addition to oncogenic effects, dysfunction or gene duplication of the Hippo pathway results in a poor prognosis due to epithelial-mesenchymal transformation of epithelial cells, stem cell transformation, and increased drug resistance. Notably, the TAZ-CAMTA1 fusion is specific to EHE, and genetic alterations in the Hippo pathway other than this fusion gene are absent in EHE. The TAZ-CAMTA1 fusion is a promising therapeutic target. This review summarizes recent advances in EHE, focusing on the role of the Hippo-YAP/TAZ pathway in EHE and its potential as a therapeutic target for drug development.
上皮样血管内皮细胞瘤（EHE）是一种罕见的起源于血管内皮细胞的恶性血管肿瘤。本研究深入探讨了 EHE 的分子机制，特别关注 Hippo-YAP/TAZ 通路。EHE 在分子上表现为转录共激活因子与 PDZ 结构域（TAZ）-钙调蛋白结合转录激活因子 1（CAMTA1）或 Yes 相关蛋白（YAP）-转录因子 E3（TFE3）融合。YAP/TAZ，一种转录共激活因子，与转录因子结合并调节基因表达。YAP/TAZ 及其上游 Hippo 通路参与细胞增殖和细胞接触抑制，调节器官大小和致癌作用。除了致癌作用外，Hippo 通路的功能障碍或基因重复导致上皮细胞上皮-间充质转化、干细胞转化和耐药性增加，从而导致预后不良。值得注意的是，TAZ-CAMTA1 融合是 EHE 的特异性，而 Hippo 通路中除了这种融合基因之外的其他遗传改变在 EHE 中不存在。TAZ-CAMTA1 融合是一个有前途的治疗靶点。本综述总结了 EHE 的最新进展，重点介绍了 Hippo-YAP/TAZ 通路在 EHE 中的作用及其作为药物开发治疗靶点的潜力。
