Stathmin/oncoprotein 18, a microtubule regulatory protein, is required for survival of both normal and cancer cell lines lacking the tumor suppressor, p53
Stathmin/oncoprotein 18, a microtubule regulatory protein, is required for survival of both normal and cancer cell lines lacking the tumor suppressor, p53
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DOI：
10.4161/cbt.9.9.11430
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发表时间：
2010-05-01
影响因子：
3.6
通讯作者：
Cassimeris, Lynne
中科院分区：
文献类型：
--
作者：
Carney, Bruce K.;Cassimeris, Lynne
Stathmin 是一种微管调节蛋白，在许多癌症中过度表达，并且是多种癌细胞系生存所必需的。在一项乳腺癌细胞系研究中，1 提出 stathmin 是缺乏 p53 的细胞存活所必需的，但这一假设并未得到直接检验。在这里，我们通过检查缺乏 stathmin、p53 或这两种蛋白的细胞中的细胞存活率来检验他们的假设。比较 TP53 基因型不同的 HCT116 结肠癌细胞系，stathmin 消耗仅导致缺乏 p53 的细胞显着死亡。作为第二个实验系统，我们比较了 HeLa 细胞中 stathmin 消耗的影响，由于 HP V E6 蛋白的表达，HeLa 细胞通常缺乏可检测水平的 p53。 Stathmin 耗尽导致大部分 HeLa 细胞死亡。通过消除 HP V E6 来恢复 p53，可将 HeLa 细胞从 Stathmin 消除引起的死亡中拯救出来。在 Stathmin 耗尽的 HCT116(p53-/-) 细胞中检测到裂解的 PARP，并且 Stathmin 耗尽的 HeLa 细胞中的细胞死亡被 caspase 抑制剂 Z-VAD-FMK 阻断，这与细胞凋亡一致。缺乏 p53 的细胞依赖 Stathmin 的存活并不局限于癌细胞，因为这两种蛋白都是正常人成纤维细胞存活所必需的。在 HCT116 和 HeLa 细胞中，stathmin 和 p53 的消耗会导致细胞周期延迟至 G(2)。我们的结果表明，在缺乏 p53 的细胞中，stathmin 是细胞存活所必需的，这表明 Stathmin 耗竭可用于治疗性地诱导没有功能性 p53 的肿瘤的细胞凋亡。
Stathmin, a microtubule regulatory protein, is overexpressed in many cancers and required for survival of several cancer lines. In a study of breast cancer cell lines, 1 proposed that stathmin is required for survival of cells lacking p53, but this hypothesis was not tested directly. Here we tested their hypothesis by examining cell survival in cells depleted of stathmin, p53 or both proteins. Comparing HCT116 colon cancer cell lines differing in TP53 genotype, stathmin depletion resulted in significant death only in cells lacking p53. As a second experimental system, we compared the effects of stathmin depletion from HeLa cells, which normally lack detectable levels of p53 due to expression of the HP V E6 protein. Stathmin depletion caused a large percentage of HeLa cells to die. Restoring p53, by depletion of HP V E6, rescued HeLa cells from stathmin-depletion induced death. Cleaved PARP was detected in HCT116(p53-/-) cells depleted of stathmin and cell death in stathmin-depleted HeLa cells was blocked by the caspase inhibitor Z-VAD-FMK, consistent with apoptotic death. The stathmin-dependent survival of cells lacking p53 was not confined to cancerous cells because both proteins were required for survival of normal human fibroblasts. In HCT116 and HeLa cells, depletion of both stathmin and p53 leads to a cell cycle delay through G(2). Our results demonstrate that stathmin is required for cell survival in cells lacking p53, suggesting that stathmin depletion could be used therapeutically to induce apoptosis in tumors without functional p53.