Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors
文献类型：期刊论文
| 作者 | Zhang, Xu5,6; Wang, Yuxiang6; Zhang, Xi6; Shen, Yanyan6; Yang, Kang4; Ma, Qingyang3; Qiao, Yuemei2; Shi, Jiajie6; Wang, Yi6; Xu, Lan6 |
| 刊名 | SIGNAL TRANSDUCTION AND TARGETED THERAPY
 |
| 出版日期 | 2023-04-12 |
| 卷号 | 8期号:1页码:153 |
| DOI | 10.1038/s41392-023-01359-x |
| 文献子类 | Article |
| 英文摘要 | Phosphatidylinositol 3-kinase alpha (PI3K alpha) inhibitors are currently evaluated for the therapy of esophageal squamous cell carcinoma (ESCC). It is of great importance to identify potential biomarkers to predict or monitor the efficacy of PI3K alpha inhibitors in an aim to improve the clinical responsive rate in ESCC. Here, ESCC PDXs with CCND1 amplification were found to be more sensitive to CYH33, a novel PI3K alpha-selective inhibitor currently in clinical trials for the treatment of advanced solid tumors including ESCC. Elevated level of cyclin D1, p21 and Rb was found in CYH33-sensitive ESCC cells compared to those in resistant cells. CYH33 significantly arrested sensitive cells but not resistant cells at G1 phase, which was associated with accumulation of p21 and suppression of Rb phosphorylation by CDK4/6 and CDK2. Hypo-phosphorylation of Rb attenuated the transcriptional activation of SKP2 by E2F1, which in turn hindered SKP2-mediated degradation of p21 and reinforced accumulation of p21. Moreover, CDK4/6 inhibitors sensitized resistant ESCC cells and PDXs to CYH33. These findings provided mechanistic rationale to evaluate PI3K alpha inhibitors in ESCC patients harboring amplified CCND1 and the combined regimen with CDK4/6 inhibitors in ESCC with proficient Rb. |
| WOS关键词 | GENETIC-VARIANTS ; PI3K PATHWAY ; CYCLIN D ; CANCER ; COMBINATION ; DERIVATIVES ; ALPELISIB ; 11Q13.3 ; POTENT ; P21 |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000968047300001 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309644]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Yi; Ding, Jian; Meng, Linghua |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Key Lab Tissue Microenvironm & Tumor, Shanghai 200031, Peoples R China; 4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China; 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Xu,Wang, Yuxiang,Zhang, Xi,et al. Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(1):153. |
| APA | Zhang, Xu.,Wang, Yuxiang.,Zhang, Xi.,Shen, Yanyan.,Yang, Kang.,...&Meng, Linghua.(2023).Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors.SIGNAL TRANSDUCTION AND TARGETED THERAPY,8(1),153. |
| MLA | Zhang, Xu,et al."Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors".SIGNAL TRANSDUCTION AND TARGETED THERAPY 8.1(2023):153. |
入库方式： OAI收割
来源：上海药物研究所
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