The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth.

The CSB repair factor is overexpressed in cancer cells, increases apoptotic resistance, and promotes tumor growth.
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DOI:
10.1016/j.dnarep.2013.01.008
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发表时间:
2013-04-01
期刊:
影响因子:
3.8
通讯作者:
Proietti-De-Santis, Luca
Proietti-De-Santis, Luca
中科院分区:
医学3区
文献类型:
--
作者:
Caputo, Manuela;Frontini, Mattia;Velez-Cruz, Renier;Nicolai, Serena;Prantera, Giorgio;Proietti-De-Santis, Luca

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CSB蛋白在癌细胞和组织中过表达。CSB在癌细胞中的抑制导致细胞增殖停滞和凋亡显著增加。CSB的下调使癌细胞对抗癌化疗药物高度敏感。在目前的研究中,我们发现,许多来自不同组织的癌细胞系显示出Cockayne综合征组B(CS B)蛋白的表达显著增加,这是一种DNA修复因子,最近被证明与细胞稳健性有关。此外,我们证明了通过反义技术消融这种蛋白质通过急剧减少细胞增殖和大量诱导凋亡对肿瘤细胞产生破坏性影响,而非转化细胞不受影响。最后,癌细胞中CSB的抑制使这些细胞对各种常用的癌症化疗剂过敏。基于这些结果,我们得出结论,癌细胞过度表达CSB蛋白,以提高其抗凋亡能力。CSB抑制仅特异性影响癌细胞而不损害健康细胞的事实表明,CSB可能是开发新抗癌疗法的非常有吸引力的靶点。
► CSB protein is overexpressed in cancer cells and tissues. ► Suppression of CSB in cancer cells resulted in cell proliferation arrest and marked increase in apoptosis. ► Down-regulation of CSB made cancer cells hypersensitive to anti-cancer chemotherapeutic drugs. In the present study we show that a number of cancer cell lines from different tissues display dramatically increased expression of the Cockayne Syndrome group B (CSB) protein, a DNA repair factor, that has recently been shown to be involved in cell robustness. Furthermore, we demonstrated that ablation of this protein by antisense technology causes devastating effects on tumor cells through a drastic reduction of cell proliferation and massive induction of apoptosis, while non-transformed cells remain unaffected. Finally, suppression of CSB in cancer cells makes these cells hypersensitive to a variety of commonly used cancer chemotherapeutic agents. Based on these results, we conclude that cancer cells overexpress CSB protein in order to enhance their anti-apoptotic capacity. The fact that CSB suppression specifically affects only cancerous cells, without harming healthy cells, suggests that CSB may be a very attractive target for the development of new anticancer therapies.
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