机制(生物学)
上皮-间质转换
癌症
脂肪生成
脂肪组织
癌细胞
计算生物学
转移
生物
癌症干细胞
癌症研究
化学
计算机科学
遗传学
物理
生物化学
量子力学
作者
Zihao Chen,Jia Lu,Xing‐Ming Zhao,Haiyang Yu,Chunhe Li
标识
DOI:10.1002/advs.202404854
摘要
Abstract Cancer is a systemic heterogeneous disease involving complex molecular networks. Tumor formation involves an epithelial‐mesenchymal transition (EMT), which promotes both metastasis and plasticity of cancer cells. Recent experiments have proposed that cancer cells can be transformed into adipocytes via a combination of drugs. However, the underlying mechanisms for how these drugs work, from a molecular network perspective, remain elusive. To reveal the mechanism of cancer‐adipose conversion (CAC), this study adopts a systems biology approach by combing mathematical modeling and molecular experiments, based on underlying molecular regulatory networks. Four types of attractors are identified, corresponding to epithelial (E), mesenchymal (M), adipose (A) and partial/intermediate EMT (P) cell states on the CAC landscape. Landscape and transition path results illustrate that intermediate states play critical roles in the cancer to adipose transition. Through a landscape control approach, two new therapeutic strategies for drug combinations are identified, that promote CAC. These predictions are verified by molecular experiments in different cell lines. The combined computational and experimental approach provides a powerful tool to explore molecular mechanisms for cell fate transitions in cancer networks. The results reveal underlying mechanisms of intermediate cell states that govern the CAC, and identified new potential drug combinations to induce cancer adipogenesis.
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