CLCA2调节EMT-MET表型转换在宫颈癌侵袭转移中的机制研究
批准号:
81960515
项目类别:
地区科学基金项目
资助金额:
35.0 万元
负责人:
王芳
依托单位:
学科分类:
肿瘤复发与转移
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
王芳
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中文摘要
宫颈癌是女性常见的恶性肿瘤之一,尽管宫颈癌的手术和放化治疗取得了很大的进展,但转移及复发患者的预后仍不满意。近年来研究发现,上皮-间充质转化(EMT)在各种上皮肿瘤的侵袭转移中起着关键作用。我们前期工作发现,中药单体异紫堇碱可上调CLCA2表达诱导逆上皮-间充质转化(MET)而发挥抑癌效应,但具体机制尚不明确。本项目在前期研究的基础上,拟通过细胞实验、动物实验及临床实验进行以下研究:(1)通过对宫颈癌细胞株CLCA2基因过表达和沉默及其荷瘤裸鼠实验,评价CLCA2在宫颈癌细胞系侵袭转移中的作用;(2)采用转录组和蛋白质组等组学手段,解析CLCA2对宫颈癌EMT-MET表型转换的调控及信号通路的影响;(3)通过对宫颈癌患者临床组织标本和临床资料进行收集和检测分析,探索CLCA2表达在宫颈癌诊疗中的临床意义。本研究对揭示宫颈癌进展和转移的分子机制,寻找新的分子治疗靶点有重要的意义。
英文摘要
Cervical cancer is one of the common malignant tumors in women. Although the surgery and radiotherapy of cervical cancer have made great progress, the prognosis of patients with metastasis and recurrence is far from satisfactory. Recent studies have found that epithelial-mesenchymal transition (EMT) plays a key role in the invasion and metastasis of various epithelial tumors. Our previous work shows that the traditional Chinese medicine monomer Isocorydine could up-regulate CLCA2 expression to induce inverse epithelial-mesenchymal transition (MET) and exert a tumor suppressing effect, but its specific mechanism remains unclear. Based on the previous studies, this project intends to address the following issues through cell experiments, animal experiments and clinical experiments: (1) The evaluation of the the role of CLCA2 in invasion and metastasis of cervical cancer cell lines by overexpressing and silencing CLCA2 gene respectively in cervical cancer cell lines and its tumor-bearing nude mice; (2) Analysis of the influence of CLCA2 on the regulation of EMT-MET phenotype transition and the signaling pathway in cervical cancer by transcriptome and proteomics; (3) Exploration of the clinical significance of the expression of CLCA2 on the outcome of cervical cancer treatment by collecting and analyzing the clinical tissue specimens and clinical data of cervical cancer. This study is of great significance for revealing the molecular mechanisms of progression and metastasis of cervical cancer and searching for new molecular therapeutic targets.
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CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.
CLCA2过表达通过灭活ERK/JNK/p38-MAPK信号通路来抑制宫颈癌细胞中的上皮 - 间质转变。
DOI:10.1186/s12860-022-00440-7
发表时间:2022-10-25
期刊:BMC molecular and cell biology
影响因子:2.8
作者:
通讯作者:
DOI:--
发表时间:2022
期刊:医学综述
影响因子:--
作者:辛文虎;王芳
通讯作者:王芳
DOI:10.1016/j.tjog.2021.03.016
发表时间:2021-05-06
期刊:TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY
影响因子:2.1
作者:Yang, Xin;Cao, Jin-Long;Wang, Fang
通讯作者:Wang, Fang
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