Hedgehog signaling mechanism and role in cancer.
Hedgehog signaling mechanism and role in cancer.
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DOI：
10.1016/j.semcancer.2021.04.003
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发表时间：
2022-10
影响因子：
14.5
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Jiang J
通过进化上保守的信号通路进行的细胞间通讯控制着胚胎发育和成年组织的动态平衡。这些信号通路的解除调控与包括癌症在内的一系列人类疾病有关。其中一条途径是Hedgehog(HH)途径，它最初是在果蝇中发现的，后来发现在人类发育和疾病中发挥着重要作用。HH通路的异常激活是基底细胞癌和髓母细胞瘤的主要驱动因素。HH通过一条非常保守的信号转导途径发挥其生物学影响，从GPCR族跨膜蛋白Smoothens(Smo)的激活到潜在的锌指转录因子Gli/Ci蛋白从其抑制物(Glir/Cir)转化为激活物(Glia/CIA)。来自模式生物和人类患者的研究为HH信号转导机制提供了深刻的见解，揭示了HH信号在广泛的人类癌症中的作用，并提出了在癌症治疗中针对这一途径的多种策略。
Cell-cell communication through evolutionarily conserved signaling pathways governs embryonic development and adult tissue homeostasis. Deregulation of these signaling pathways has been implicated in a wide range of human diseases including cancer. One such pathway is the Hedgehog (Hh) pathway, which was originally discovered in Drosophila and later found to play a fundamental role in human development and diseases. Abnormal Hh pathway activation is a major driver of basal cell carcinomas (BCC) and medulloblastoma. Hh exerts it biological influence through a largely conserved signal transduction pathway from the activation of the GPCR family transmembrane protein Smoothened (Smo) to the conversion of latent Zn-finger transcription factors Gli/Ci proteins from their repressor (GliR/CiR) to activator (GliA/CiA) forms. Studies from model organisms and human patients have provided deep insight into the Hh signal transduction mechanisms, revealed roles of Hh signaling in a wide range of human cancers, and suggested multiple strategies for targeting this pathway in cancer treatment.
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