FATS调控乳腺癌放疗敏感性的机制研究
结题报告
批准号:
81702629
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
张军
依托单位:
学科分类:
H1816.肿瘤放射治疗
结题年份:
2020
批准年份:
2017
项目状态:
已结题
项目参与者:
钱晓龙、齐立强、张铁梅、金钊、仇丽、吴楠、张海莲
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中文摘要
本课题组在前期研究中克隆并命名新的脆性位点基因FATS,并发现与人类肿瘤密切相关。在乳腺癌中我们发现FATS显著下调,过表达FATS增加乳腺癌细胞放疗敏感性。对临床病例研究发现:FATS高表达有更好的预后,FATS是独立预后因素,为研究放疗敏感性奠定了基础。进一步研究发现,FATS可激活p53信号通路,进而促进放疗诱导的细胞凋亡,增加放疗敏感性。但乳腺癌中FATS如何调控p53信号通路进而影响放疗敏感性尚不明确。本项目将在前期基础上,从分子、细胞、模型小鼠及临床患者四个方面深入研究FATS如何调控p53信号通路进而影响放疗敏感性的分子机制,并探讨FATS作为预测乳腺癌放疗敏感性分子靶标的可能性,从而明确FATS放疗增敏作用并阐明其可能的分子机制,本课题的开展将为开发与FATS相关靶向治疗应用于乳腺癌放疗增敏提供理论基础及实验依据,为乳腺癌放射治疗增加新的内容,提供新的思路,具有重要意义。
英文摘要
we found a new evolutionary conserved fragile sites gene, which was named fragile-site associated tumor suppressor (FATS), and firstly was cloned FATS internationally. Previous studies found that FATS located FRA10F, closely associated with human tumors. Our preliminary data showed that FATS was significantly downregulated in breast cancer and its expression positively correlated with radiosensitivity of breast cancer cells. Radiotherapy significantly increased DFS of breast cancer patients with positive FATS status in.comparison to that of FATS-negative patients. Multivariate cox regression analysis revealed that FATS status was a more valuable predictor of DFS for breast cancer patients receiving radiotherapy. Further study revealed that FATS activated p53 signaling, and subsequently resulted in enhancement of radiation- induced apoptosis. However, much more exact molecular mechanisms about how FATS activated.p53 signaling and radiosensitized breast cancer remain to be further investigated. Therefore, based on these findings, this project will deeply investigate the mechanisms of FATS in inhibiting p53 signaling and sensitizing breast cancer to radiation by employing molecular biology, cell biology techniques, nude mice xenograftic model and clinical sample. Futhermore we will investigate the potential of FATS as a marker for patients radiosensitivity predicting. This project will offer the theocratic basis and experimental evidence for the application of FATS-related targeted therapy into the radiation therapy of breast cancer. All in all, this research would provide us new target and therapeutic strategy for improving the radiotherapy outcome of breast cancer, which is of great clinical significance.
放射治疗作为目前乳腺癌综合治疗的重要组成部分是控制乳腺癌非常有效的治疗方案,但是患者放疗疗效存在个体差异,究其原因可能由于其放疗敏感性差异所导致,本研究课题基于我们的预实验结果及前期已发表研究的基础上,以过表达和敲低 FATS 的乳腺癌细胞为模型,采用多种体外、体内实验方法,揭示了 FATS 可以增强乳腺癌细胞的放疗敏感性,促进放射治疗对肿瘤的杀伤作用;FATS 调控乳腺癌放疗敏感性的分子机制是p53依赖性的,因此 FATS 可以作为预测患者放疗敏感性的分子标志及指导个性化的个体放疗方案的实施。本课将丰富放疗敏感性分子靶标研究内容,FATS 将是一个全新的与乳腺癌放疗敏感性相关的重要诊断标志物和治疗靶点,这将为临床乳腺癌诊断、预后判断及个体化放射治疗提供理论及实验依据,具有重要理论意义与临床应用价值。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Silencing of syndecan-binding protein enhances the inhibitory effect of tamoxifen and increases cellular sensitivity to estrogen.
沉默多聚糖结合蛋白可增强他莫昔芬的抑制作用并增加细胞对雌激素的敏感性
DOI:10.20892/j.issn.2095-3941.2017.0122
发表时间:2018-03
期刊:Cancer biology & medicine
影响因子:5.5
作者:Zhang J;Qian X;Liu F;Guo X;Gu F;Fu L
通讯作者:Fu L
Intracystic papillary carcinoma of the breast: Experience of a major Chinese cancer center
乳腺癌囊内乳头状癌:中国主要癌症中心的经验
DOI:10.1016/j.prp.2018.01.006
发表时间:2018-04-01
期刊:PATHOLOGY RESEARCH AND PRACTICE
影响因子:2.8
作者:Zhang, Jun;Zhang, Tiemei;Gu, Lin
通讯作者:Gu, Lin
Functional analysis and clinical significance of the isocitrate dehydrogenase 2 gene in papillary thyroid carcinoma
甲状腺乳头状癌异柠檬酸脱氢酶2基因的功能分析及临床意义
DOI:10.2147/cmar.s194920
发表时间:2019-05
期刊:Cancer Management and Research
影响因子:3.3
作者:Zhang Jun;Hu Linfei;Wang Huijuan;Zhi Jingtai;Hou Xiukun;Wu Yu;Zheng Xiangqian;Gao Ming
通讯作者:Gao Ming
FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer.
FATS 通过促进非小细胞肺癌中 ERβ 依赖方式的 ODC 降解来调节多胺生物合成。
DOI:10.1038/s41419-020-03052-1
发表时间:2020-10-09
期刊:Cell death & disease
影响因子:9
作者:Qiu L;Hu L;Wang H;Li J;Ruan X;Sun B;Zhi J;Zheng X;Gu L;Gao M;Kong P;Zhang J
通讯作者:Zhang J
新E3泛素连接酶FATS在肿瘤和小鼠胚胎血管生成中的功能及机制研究
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    54.7万元
  • 批准年份:
    2021
  • 负责人:
    张军
  • 依托单位:
国内基金
海外基金