The atypical cyclin CNTD2 promotes colon cancer cell proliferation and migration.

The atypical cyclin CNTD2 promotes colon cancer cell proliferation and migration.
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DOI:
10.1038/s41598-018-30307-x
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发表时间:
2018-08-07
期刊:
影响因子:
4.6
通讯作者:
Clotet J
Clotet J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sánchez-Botet A;Gasa L;Quandt E;Hernández-Ortega S;Jiménez J;Mezquita P;Carrasco-García MÀ;Kron SJ;Vidal A;Villanueva A;Ribeiro MPC;Clotet J

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结直肠癌 (CRC) 是全球最常见的癌症之一,其中 8-10% 的肿瘤存在 BRAF (V600E) 突变。细胞周期蛋白是已知的在许多癌症中失调的癌基因,但非典型细胞周期蛋白的新亚家族的作用仍然难以捉摸。在这里,我们对人类CRC肿瘤和几种细胞系中八种非典型细胞周期蛋白的蛋白表达水平进行了系统分析,发现与邻近的正常组织相比,CNTD2在CRC组织中显着上调。 CNTD2 在 CRC 细胞系中的过表达增加了其增殖能力和迁移能力,以及球体形成能力和贴壁依赖性生长。此外,CNTD2 在野生型 BRAF 的 CRC 异种移植模型中增加体内肿瘤生长。因此,CNTD2的下调显着减少了野生型BRAF CRC细胞的增殖,这表明CNTD2可能代表一个新的预后因素和CRC治疗中有希望的药物靶点。
Colorectal cancer (CRC) is one of the most common cancers worldwide, with 8–10% of these tumours presenting a BRAF (V600E) mutation. Cyclins are known oncogenes deregulated in many cancers, but the role of the new subfamily of atypical cyclins remains elusive. Here we have performed a systematic analysis of the protein expression levels of eight atypical cyclins in human CRC tumours and several cell lines, and found that CNTD2 is significantly upregulated in CRC tissue compared to the adjacent normal one. CNTD2 overexpression in CRC cell lines increases their proliferation capacity and migration, as well as spheroid formation capacity and anchorage-independent growth. Moreover, CNTD2 increases tumour growth in vivo on xenograft models of CRC with wild-type BRAF. Accordingly, CNTD2 downregulation significantly diminished the proliferation of wild-type BRAF CRC cells, suggesting that CNTD2 may represent a new prognostic factor and a promising drug target in the management of CRC.
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