Liu Yuechao, Xing Ying, Cai Li
The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.
Zhongguo Fei Ai Za Zhi. 2017 Sep 20;20(9):629-634. doi: 10.3779/j.issn.1009-3419.2017.09.07.
Lung cancer is the leading cause of cancer related mortality in the world, with more than 1 million deaths per year, accounting for about one fifth of all cancer deaths worldwide. Over the past years, lung cancer treatment has been based on surgery, radiation therapy, chemotherapy, targeted therapies, and immunotherapy, but the improvement is not very perfect. Therefore, it has become clear that additional therapeutic strategies are urgently required to provide an improved survival benefit for patients. In recent years, Hippo signaling pathway has become a popular direction in the field of cancer research. When the Hippo pathway is active, the core Hippo kinase, such as MST/MOB and LATS1/2, inhibit the two transcriptional co-activators, YAP/TAZ. And YAP/TAZ are phosphorylated and sequestered in the cytoplasm. Dysregulation of the Hippo pathway drives multiple aspects of lung tumor initiation and progression. Moreover, the potential value of this pathway is getting more and more prevalent in clinical application. In this review, we summarize the molecular mechanism and the core components, upstream or downstream targets of Hippo signaling pathway which contribute the formation of lung cancer and discuss the therapeutic potential of targeted strategies in lung cancer. Additionally, we highlight the prospect of research on Hippo signaling pathway in the future.
肺癌是全球癌症相关死亡的主要原因，每年有超过100万人死亡，约占全球所有癌症死亡人数的五分之一。在过去几年中，肺癌治疗一直基于手术、放射治疗、化疗、靶向治疗和免疫治疗，但改善效果并不十分理想。因此，显然迫切需要额外的治疗策略，为患者提供更好的生存获益。近年来，Hippo信号通路已成为癌症研究领域一个热门方向。当Hippo通路激活时，核心Hippo激酶，如MST/MOB和LATS1/2，会抑制两种转录共激活因子YAP/TAZ。YAP/TAZ会被磷酸化并滞留在细胞质中。Hippo通路失调会推动肺肿瘤发生和进展的多个方面。此外，该通路的潜在价值在临床应用中越来越普遍。在本综述中，我们总结了Hippo信号通路的分子机制、核心成分、上游或下游靶点，这些因素促成了肺癌的形成，并讨论了肺癌靶向治疗策略的潜力。此外，我们还强调了未来Hippo信号通路的研究前景。
