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中华乳腺病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (05) : 300 -304. doi: 10.3877/cma.j.issn.1674-0807.2016.05.010

综述

脯氨酰顺反异构酶Pin1 在乳腺癌中的研究进展
陈阳1, 姚燕丹2, 罗曼莉2, 黄松音1,()   
  1. 1.510120 广州,中山大学孙逸仙纪念医院检验科
    2.510120 广州,中山大学孙逸仙纪念医院乳腺肿瘤医学部
  • 收稿日期:2016-03-16 出版日期:2016-10-01
  • 通信作者: 黄松音
  • 基金资助:
    国家自然科学基金项目(81572890)广东省科技计划项目(2014A050503029,2012A032500003)广州市科技计划项目(2014J4100166)

Prolyl cis-trans isomerase Pin1 in breast cancer

Yang Chen, Yandan Yao, Manli Luo, Songying Huang()   

  • Received:2016-03-16 Published:2016-10-01
  • Corresponding author: Songying Huang
引用本文:

陈阳, 姚燕丹, 罗曼莉, 黄松音. 脯氨酰顺反异构酶Pin1 在乳腺癌中的研究进展[J/OL]. 中华乳腺病杂志(电子版), 2016, 10(05): 300-304.

Yang Chen, Yandan Yao, Manli Luo, Songying Huang. Prolyl cis-trans isomerase Pin1 in breast cancer[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(05): 300-304.

蛋白磷酸化信号通过影响蛋白的构象变化而调控细胞周期、细胞增殖和分化等许多细胞内过程。 脯氨酰顺反异构酶Pin1(protein interaction with NIMA1)特异性识别并催化蛋白分子中磷酸化丝氨酸/苏氨酸-脯氨酸(pSer/Thr-Pro)的构象变化,进而控制蛋白分子与底物的作用、蛋白分子之间的相互作用以及影响底物稳定性等。 作为蛋白分子的“时间控制器”,Pin1 参与多个肿瘤发生通路。 在细胞表型方面,Pin1 高表达可抑制肿瘤细胞凋亡,促进肿瘤细胞生长、侵袭和转移,促进肿瘤血管生成,引起治疗药物耐受,以及促进肿瘤干细胞自我更新;在分子机制方面,Pin1 可促进癌基因转录,提高其蛋白活性,抑制其降解,还可降低抑癌基因的表达或活性。 此外,Pin1 基因敲除小鼠的正常乳腺干细胞以及孕期乳腺上皮细胞的增殖都受到抑制。 在临床研究中,Pin1 的表达水平也与乳腺癌的发生及预后密切相关。 因此,Pin1 作为治疗乳腺癌的新靶标具有良好的应用前景。

图1 Pin1 与TAMR 耐药[13,25-35]、曲妥珠单克隆抗体耐药[11,13,36-40]及BCSCs[31,41-49]的关系 注:BCSCs 代表乳腺癌干细胞;CDK10 代表周期依赖性激酶10;c-Jun 为一种癌基因;E6AP 为一种泛素连接酶;EMT 代表上皮-间质转化;ERBB2:即HER-2;ERK1/2 代表细胞外信号调节激酶1/2;FAS 代表脂肪酸合酶;Fbxw7α 为一种泛素酶;GSB-3β 代表糖原合成酶激酶3β;HIF-1α 代表缺氧诱导因子-1α;MAP1-LC3 代表微管相关蛋白1 的轻链3;MAPK 代表丝裂原活化蛋白激酶;MEK1 代表丝裂原活化蛋白激酶的激酶1; MKP3 代表丝裂原相关蛋白激酶的磷酸酶3; mTOR 代表雷帕霉素靶蛋白;N1-ICD 代表Notch1 胞内结构域;NF-κB 代表核因子κB;PI3K 代表磷酸肌醇3-激酶;PP2A 代表蛋白磷酸酶2A;PTEN 为一种抑癌基因;Rab2A 为一种小GTPase;Raf-1 为一种丝氨酸/苏氨酸蛋白激酶;RAS 为一种癌基因;SGK1 代表糖皮质激素诱导的蛋白激酶1;Smad 为TGF-β 超家族胞内信号途径的关键效应分子;SMRT 代表维甲酸和甲状腺激素受体的沉默受体;TAMR 代表他莫昔芬耐药;ZEB1 为一种锌指结构蛋白;绿色带箭头线条表示促进作用; 红色带横杆线条表示抑制作用; Ub 表示泛素化; P 表示磷酸化
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