中文版 | English
题名

PINCH-1在皮肤癌发生发展中的作用及其分子机制的研究

其他题名
MOLECULAR MECHANISMS OF PINCH-1 IN THE DEVELOPMENT AND PROGRESSION OF SKIN CANCER
姓名
姓名拼音
JIANG Kun
学号
12032139
学位类型
硕士
学位专业
0710 生物学
学科门类/专业学位类别
07 理学
导师
邓怿
导师单位
生命科学学院
论文答辩日期
2023-05-12
论文提交日期
2023-07-03
学位授予单位
南方科技大学
学位授予地点
深圳
摘要

PINCH-1是细胞质中参与细胞细胞外基质(ECM)黏附机制主要成分之一,常在癌症中过表达。然而,PINCH-1在肿瘤中的作用和机制仍有待研究。我们发现PINCH-1可以调节NEDD4介导的IGF-1受体(IGF-1R)的降解,并影响皮肤肿瘤的生长。IGF-1R信号通路在肿瘤的发生、发展中起着重要的调控作用。GRB10结合E3泛素连接酶NEDD4并促进IGF-1R的泛素化、内化和降解。我们研究发现PINCH-1与NEDD4相互作用,抑制NEDD4与GRB10结合,从而抑制IGF-1R降解。降低皮肤癌细胞中PINCH-1的表达,IGF-1R蛋白水平下降,抑制细胞增殖。重新表达PINCH-1可有效逆转PINCH-1缺失导致的IGF-1R表达抑制和细胞增殖抑制。同样,在化学诱导的皮肤肿瘤动物模型中,keratin 5阳性细胞的PINCH-1,发生肿瘤的概率显著降低。这些结果揭示了PINCH-1-NEDD4-IGF-1R信号轴在皮肤肿瘤进展中至关重要,并为皮肤肿瘤的治疗控制提供了新的策略。

 

 

 

关键词
语种
中文
培养类别
独立培养
入学年份
2020
学位授予年份
2023-06
参考文献列表

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姜坤. PINCH-1在皮肤癌发生发展中的作用及其分子机制的研究[D]. 深圳. 南方科技大学,2023.
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