Xu Sunwang, Zhan Ming, Wang Jian
Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Cell Death Discov. 2017 Nov 27;3:17069. doi: 10.1038/cddiscovery.2017.69. eCollection 2017.
Gallbladder cancer (GBC), with late diagnosis, rapid disease progression and early metastasis, is a highly aggressive malignant tumor found worldwide. Patients with GBC have poor survival, low curative resection rates and early recurrence. For such a lethal tumor, uncovering the mechanisms and exploring new strategies to prevent tumor progression and metastasis are critically important. Epithelial-to-mesenchymal transition (EMT) has a prominent role in the early steps of tumor progression and metastasis by initiating polarized epithelial cell transition into motile mesenchymal cells. Accumulating evidence suggests that EMT can be modulated by the cooperation of multiple mechanisms affecting common targets. Signaling pathways, transcriptional and post-transcriptional regulation and epigenetic alterations are involved in the stepwise EMT regulatory network in GBC. Loss of epithelial markers, acquisition of mesenchymal markers and dysregulation of EMT-inducing transcription factors (EMT-TFs) have been observed and are associated with the clinicopathology and prognosis of GBC patients. Therefore, EMT may be a detectable and predictable event for predicting GBC progression and metastasis in the clinic. In this review, we will provide an overview of EMT from the clinical evidence to cellular regulatory networks that have been studied thus far in clinical and basic GBC studies.
胆囊癌（GBC）诊断较晚，疾病进展迅速且早期易发生转移，是一种在全球范围内发现的侵袭性很强的恶性肿瘤。GBC患者生存率低，根治性切除率低且早期复发率高。对于这样一种致命的肿瘤，揭示其机制并探索预防肿瘤进展和转移的新策略至关重要。上皮-间质转化（EMT）在肿瘤进展和转移的早期阶段起着重要作用，它可使极化的上皮细胞转变为具有运动能力的间质细胞。越来越多的证据表明，EMT可通过影响共同靶点的多种机制协同作用进行调节。信号通路、转录和转录后调控以及表观遗传改变均参与了GBC中EMT的逐步调控网络。已观察到上皮标志物的丢失、间质标志物的获得以及EMT诱导转录因子（EMT-TFs）的失调，且这些与GBC患者的临床病理特征及预后相关。因此，EMT可能是临床上预测GBC进展和转移的一个可检测且可预测的事件。在本综述中，我们将从临床证据到迄今为止在临床和基础GBC研究中所研究的细胞调控网络，对EMT进行概述。
