The BAX/BAK-like protein BOK is a prognostic marker in colorectal cancer.

The BAX/BAK-like protein BOK is a prognostic marker in colorectal cancer.
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DOI:
10.1038/s41419-017-0140-2
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发表时间:
2018-01-26
影响因子:
9
通讯作者:
Prehn JHM
Prehn JHM
中科院分区:
生物学1区
文献类型:
--
作者:
Carberry S;D'Orsi B;Monsefi N;Salvucci M;Bacon O;Fay J;Rehm M;McNamara D;Kay EW;Prehn JHM

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内在或线粒体凋亡途径由 BCL-2 蛋白家族的抗凋亡和促凋亡成员的相互作用控制。这种死亡途径的激活在癌症进展和化疗反应中起着至关重要的作用。 BCL-2 相关卵巢杀手 (BOK) 拥有三个 BCL-2 同源结构域,并且已被认为与促凋亡蛋白 BAX 和 BAK 具有相似的促凋亡途径。在这项研究中,我们发现,与匹配的正常组织相比,II 期和 III 期结直肠癌患者的肿瘤中 BOK 蛋白水平降低。肿瘤中的 BOK 蛋白水平也可以预测临床结果,但令人惊讶的是,BOK 蛋白水平升高与早期疾病复发和总体生存率降低相关。我们发现 BOK 蛋白肿瘤水平与 ER 应激标记物 GRP78 或 GRP94 或与裂解的 caspase-3 没有显着相关性。相反,BOK 蛋白水平与钙网蛋白相关。这些数据表明 BOK 作为结直肠癌的预后标志物,并表明 BOK 的不同活性可能有助于癌症进展和预后。
The intrinsic or mitochondrial apoptosis pathway is controlled by the interaction of antiapoptotic and pro-apoptotic members of the BCL-2 protein family. Activation of this death pathway plays a crucial role in cancer progression and chemotherapy responses. The BCL-2-related ovarian killer (BOK) possesses three BCL-2 homology domains and has been proposed to act in a similar pro-apoptotic pathway as the pro-apoptotic proteins BAX and BAK. In this study, we showed that stage II and III colorectal cancer patients possessed decreased levels of BOK protein in their tumours compared to matched normal tissue. BOK protein levels in tumours were also prognostic of clinical outcome but increased BOK protein levels surprisingly associated with earlier disease recurrence and reduced overall survival. We found no significant association of BOK protein tumour levels with ER stress markers GRP78 or GRP94 or with cleaved caspase-3. In contrast, BOK protein levels correlated with Calreticulin. These data indicate BOK as a prognostic marker in colorectal cancer and suggest that different activities of BOK may contribute to cancer progression and prognosis.
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