Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment.
Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment.
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抑制素结构域家族在肿瘤发生中的意义及其在癌症诊断和治疗中的意义
DOI：
10.1038/s41419-018-0661-3
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发表时间：
2018-05-21
影响因子：
9
通讯作者：
He QY
中科院分区：
文献类型：
--
作者：
Yang J;Li B;He QY
禁止蛋白（PHB）最初是在大鼠肝脏中分离到的一种抗增殖基因。进化上保守的phbgene编码两种分子量为~33 kDa的人蛋白亚型PHB1和PHB2。PHB1和PHB2属于禁止蛋白结构域家族，广泛分布于线粒体、细胞核、细胞膜等不同的细胞区室中。大多数研究证实，与相应的正常组织相比，PHB1和PHB2在癌症中的表达存在差异。此外，研究证实PHB1和PHB2参与肿瘤发生的生物学过程，包括癌细胞增殖、凋亡和转移。从药用植物中提取的两种小分子抑制剂Rocaglamide （RocA）和fluorizoline被证明可直接与PHB1相互作用，从而抑制PHB与Raf-1的相互作用，阻断Raf-1/ERK信号级联反应，显著抑制癌细胞转移。此外，一种短肽ERAP和一种天然产物黄腐酚被证明可以直接靶向PHB2，并阻止雌激素依赖性癌症的癌症进展。由于癌症的诊断和治疗迫切需要更有效的生物标志物和靶点，我们在这里总结了禁止蛋白结构域家族蛋白的功能作用，重点介绍了PHB1和PHB2在肿瘤发生和癌症发展中的作用，期望靶向禁止蛋白结构域家族将为癌症治疗提供更多线索。
Prohibitin(PHB) was originally isolated and characterized as an anti-proliferative gene in rat liver. The evolutionarily conservedPHBgene encodes two human protein isoforms with molecular weights of ~33 kDa, PHB1 and PHB2. PHB1 and PHB2 belong to the prohibitin domain family, and both are widely distributed in different cellular compartments such as the mitochondria, nucleus, and cell membrane. Most studies have confirmed differential expression of PHB1 and PHB2 in cancers compared to corresponding normal tissues. Furthermore, studies verified that PHB1 and PHB2 are involved in the biological processes of tumorigenesis, including cancer cell proliferation, apoptosis, and metastasis. Two small molecule inhibitors, Rocaglamide (RocA) and fluorizoline, derived from medicinal plants, were demonstrated to interact directly with PHB1 and thus inhibit the interaction of PHB with Raf-1, impeding Raf-1/ERK signaling cascades and significantly suppressing cancer cell metastasis. In addition, a short peptide ERAP and a natural product xanthohumol were shown to target PHB2 directly and prohibit cancer progression in estrogen-dependent cancers. As more efficient biomarkers and targets are urgently needed for cancer diagnosis and treatment, here we summarize the functional role of prohibitin domain family proteins, focusing on PHB1 and PHB2 in tumorigenesis and cancer development, with the expectation that targeting the prohibitin domain family will offer more clues for cancer therapy.
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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