Cep70 overexpression stimulates pancreatic cancer by inducing centrosome abnormality and microtubule disorganization.
Cep70 overexpression stimulates pancreatic cancer by inducing centrosome abnormality and microtubule disorganization.
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Cep70过表达通过诱导中心体异常和微管解体刺激胰腺癌
DOI：
10.1038/srep21263
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发表时间：
2016-02-19
影响因子：
4.6
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Xie S;Qin J;Liu S;Zhang Y;Wang J;Shi X;Li D;Zhou J;Liu M
中心体对有丝分裂的保真度至关重要，中心体畸变与基因组不稳定性和肿瘤发生有关。据报道，中心体蛋白Cep70在多种细胞活动中发挥作用。然而，这种蛋白是否参与病理过程尚不清楚。在本研究中，我们证实Cep70在胰腺癌组织中高表达。Cep70表达与胰腺癌的组织学分级、病理肿瘤淋巴结转移分期、淋巴结转移及糖类抗原19-9水平等临床病理参数相关。Cep70缺失可显著抑制胰腺癌细胞增殖，促进凋亡细胞死亡，外源表达Cep70可挽救上述作用。Cep70还能刺激软琼脂中的菌落形成，促进小鼠肿瘤生长。我们的数据进一步表明，Cep70在胰腺癌细胞中的异位表达导致中心体蛋白（包括γ-微管蛋白和心心包蛋白）的错误定位和细胞内聚集体的形成。此外，在有丝分裂过程中，Cep70过表达导致微管解体和多极纺锤体的形成。因此，我们的研究揭示了Cep70在胰腺癌中的关键作用，并建议Cep70作为这种致命疾病的潜在生物标志物和治疗靶点。
The centrosome is crucial for mitotic fidelity and centrosome aberrations are associated with genomic instability and tumorigenesis. The centrosomal protein Cep70 has been reported to play a role in various cellular activities. However, whether this protein is involved in pathological processes remains unknown. In this study, we demonstrate that Cep70 is highly expressed in pancreatic cancer tissues. Cep70 expression correlates with clinicopathological parameters of pancreatic cancer, including histological grade, pathological tumor node metastasis stage, lymph node metastasis and carbohydrate antigen 19-9 level. Depletion of Cep70 significantly suppresses pancreatic cancer cell proliferation and promotes apoptotic cell death and exogenous expression of Cep70 can rescue the above effects. Cep70 also stimulates colony formation in soft agar and enhances tumor growth in mice. Our data further show that ectopic expression of Cep70 in pancreatic cancer cells results in the mislocalization of centrosomal proteins, including γ-tubulin and pericentrin and the formation of intracellular aggregates. In addition, Cep70 overexpression leads to microtubule disorganization and the formation of multipolar spindles during mitosis. Our study thus unravels a critical role for Cep70 in pancreatic cancer and suggests Cep70 as a potential biomarker and therapeutic target for this deadly disease.