The regulation of β-catenin activity and function in cancer: therapeutic opportunities.
The regulation of β-catenin activity and function in cancer: therapeutic opportunities.
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癌症中β-连环蛋白活性和功能的调节：治疗机会
DOI：
10.18632/oncotarget.15687
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发表时间：
2017-05-16
期刊：
影响因子：
--
通讯作者：
Hu ZW
中科院分区：
文献类型：
--
作者：
Shang S;Hua F;Hu ZW
Wnt/β-连环蛋白信号传导是一种进化上保守且多功能的途径，已知参与胚胎发育、组织稳态和多种人类疾病。该通路的异常激活会导致 β-catenin 在细胞核中积累，并促进许多癌基因（例如 c-Myc 和 CyclinD-1）的转录。因此，它有助于多种癌症的致癌和肿瘤进展，包括结肠癌、肝细胞癌、胰腺癌、肺癌和卵巢癌。 β-连环蛋白是 Wnt 信号通路的关键组成部分，在三个层次上受到严格调控：蛋白质稳定性、亚细胞定位和转录活性。揭示β-连环蛋白的调节机制将为癌症和其他疾病的发病机制提供新的见解，并为这些疾病提供新的治疗策略。本文从上述三个方面剖析了β-catenin的具体调控机制。然后我们重点关注β-连环蛋白在癌症发生、进展、休眠、免疫和癌症干细胞维持中的作用。最后，我们总结了在癌症治疗中β-连环蛋白活性药理调节剂的开发最新进展。
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer. β-Catenin is a pivotal component of the Wnt signaling pathway and it is tightly regulated at three hierarchical levels: protein stability, subcellular localization and transcriptional activity. Uncovering the regulatory mechanisms of β-catenin will provide new insights into the pathogenesis of cancer and other diseases, as well as new therapeutic strategies against these diseases. In this review we dissect the concrete regulatory mechanisms of β-catenin from three aspects mentioned above. Then we focus on the role of β-catenin in cancer initiation, progression, dormancy, immunity and cancer stem cell maintenance. At last, we summarize the recent progress in the development of agents for the pharmacological modulation of β-catenin activity in cancer therapy.