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非小细胞肺癌中 EMT 的表观遗传调控。

Epigenetic Regulation of EMT in Non-Small Cell Lung Cancer.

机构信息

Lambe Institute for Translational Research, Division of Pathology, NUI Galway, Ireland.

Molecular Oncology/Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

出版信息

Curr Cancer Drug Targets. 2018;18(1):89-96. doi: 10.2174/1568009617666170203162556.

Abstract

Lung cancer remains the most diagnosed cancer in the world, with a high mortality rate and fewer therapeutic options. The most common lung cancer is non-small cell, consisting of adenocarcinoma, squamous cell carcinoma and large cell lung carcinoma. As per all solid tumours, the changes that occur for the initiation and metastasis of lung cancer can be described using the EMT (epithelial mesenchymal transition). Cells progressing through EMT lose their epithelial cell characteristics, expressing more mesenchymal markers and are phenotypically different. The transition can be controlled by changes in various pathways, such as TGF-β, PI3K, MAPK, Hedgehog and Wnt. The changes in those pathways can be controlled epigenetically, via DNA methylation, histone modifications or changes in small/non-coding RNA. We will describe the epigenetic changes that occur in these pathways and how we can consider novel methods to generate a synthetic lethality target in an epigenetically regulated pathway in EMT.

摘要

肺癌仍然是世界上最常见的癌症,其死亡率高,治疗选择有限。最常见的肺癌是非小细胞肺癌,包括腺癌、鳞状细胞癌和大细胞肺癌。与所有实体肿瘤一样,肺癌发生起始和转移的变化可以通过 EMT(上皮间质转化)来描述。通过 EMT 进展的细胞失去上皮细胞特征,表达更多的间充质标志物,表型上也有所不同。这种转变可以通过 TGF-β、PI3K、MAPK、Hedgehog 和 Wnt 等各种途径的变化来控制。这些途径的变化可以通过表观遗传控制,如 DNA 甲基化、组蛋白修饰或小/非编码 RNA 的变化。我们将描述这些途径中发生的表观遗传变化,以及我们如何考虑在 EMT 中受表观遗传调控的途径中产生合成致死性靶标。

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