| Autor: |
Shichao Zhou, Jingyu Zang, Mei-Chun Cai, Kaiyan Ye, Jin Liu, Pengfei Ma, Jie Wu, Chenyang Dai, Haijiao Lu, Qing Zhang, Junhong Jiang, Tianqing Chu, Ying Shen, Li Tan, Guanglei Zhuang, Xiaojing Zhao, Lan Wang, Yu Zhuang, Yujie Fu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Death and Disease, Vol 15, Iss 11, Pp 1-13 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-4889 |
| DOI: |
10.1038/s41419-024-07239-8 |
| Popis: |
Abstract During targeted treatment, oncogene-addicted tumor cells often evolve from an initial drug-sensitive state through a drug-tolerant persister bottleneck toward the ultimate emergence of drug-resistant clones. The molecular basis underlying this therapy-induced evolutionary trajectory has not yet been completely elucidated. Here, we employed a multifaceted approach and implicated the convergent role of transcription factor Yin Yang 1 (YY1) in the course of diverse targeted kinase inhibitors. Specifically, pharmacological perturbation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway resulted in the downregulation of YY1 transcription, which subsequently resumed upon therapeutic escape. Failure to decrease YY1 subverted cytotoxic effects, whereas elimination of residual YY1 maximized anticancer efficacy and forestalled the emergence of drug resistance. Mechanistically, YY1 was uncovered to dictate cell cycle and autophagic programs. Immunohistochemical analysis on a wide spectrum of clinical specimens revealed that YY1 was ubiquitously expressed across lung adenocarcinomas and exhibited anticipated fluctuation in response to corresponding RTK/MAPK inhibition. These findings advance our understanding of targeted cancer management by highlighting YY1 as a determinant node in the context of genotype-directed agents. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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