抗药性
机制(生物学)
抑制器
癌细胞
信号转导
功能(生物学)
下调和上调
癌症研究
生物
癌症
计算生物学
细胞生物学
基因
遗传学
哲学
认识论
作者
Soo Min Lee,Young Ho Han,Kwang-Hyun Cho
出处
期刊:iScience
[Elsevier]
日期:2023-12-01
卷期号:26 (12): 108377-108377
标识
DOI:10.1016/j.isci.2023.108377
摘要
Tumor suppressor p53 plays a pivotal role in suppressing cancer, so various drugs has been suggested to upregulate its function. However, drug resistance is still the biggest hurdle to be overcome. To address this, we developed a deep learning model called AnoDAN (anomalous gene detection using generative adversarial networks and graph neural networks for overcoming drug resistance) that unravels the hidden resistance mechanisms and identifies a combinatorial target to overcome the resistance. Our findings reveal that the TGF-β signaling pathway, alongside the p53 signaling pathway, mediates the resistance, with THBS1 serving as a core regulatory target in both pathways. Experimental validation in lung cancer cells confirms the effects of THBS1 on responsiveness to a p53 reactivator. We further discovered the positive feedback loop between THBS1 and the TGF-β pathway as the main source of resistance. This study enhances our understanding of p53 regulation and offers insights into overcoming drug resistance.
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