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C1QBP/p32 在乳腺癌和其他癌症中的作用及其治疗潜力。

Role of C1QBP/p32 and its Therapeutic Potential in Breast Carcinoma and other Cancers.

机构信息

Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, Saitama 351-0198, Japan.

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, S117594, Singapore.

出版信息

Curr Med Chem. 2021;28(25):5048-5065. doi: 10.2174/0929867328666201231124038.

Abstract

The complement component 1, q subcomponent binding protein (C1QBP/gC1q-R/p32/HABP1/TAP/YBAP1), is a ubiquitous, multifunctional protein. C1QBP localizes mainly to mitochondria due to its N-terminal mitochondrial localization signal, but it can also be found in different subcellular compartments including the cell surface, nucleus, cytoplasm, and extracellular space. C1QBP has been reported to interact with a variety of proteins that have apparently unrelated functions. C1QBP has also been observed to interact with hyaluronic acid and RNA. These findings suggest that C1QBP has both mitochondrial and extramitochondrial functions. The C1QBP binding sites of many partner proteins are located within basic and intrinsically disordered regions of these molecules, consistent with the hypothesis that C1QBP functions as a molecular chaperone. C1QBP expression is elevated in various types of human cancers, including breast cancer. Moreover, it has been implicated in the development, progression, and metastasis of cancer cells based on loss-of-function and gain-of-function studies using cancer cell lines and xenograft models. Hence C1QBP could be a molecular target in breast cancer therapy. Studies using antibodies, tumor homing peptides such as LyP-1, and small molecules that target C1QBP warrant further investigation as C1QBP is a potential therapeutic target.

摘要

补体成分 1,q 亚基结合蛋白(C1QBP/gC1q-R/p32/HABP1/TAP/YBAP1)是一种普遍存在的多功能蛋白。由于其 N 端线粒体定位信号,C1QBP 主要定位于线粒体,但也可以在不同的亚细胞区室中发现,包括细胞膜表面、核、细胞质和细胞外空间。已经报道 C1QBP 与多种具有明显无关功能的蛋白质相互作用。C1QBP 也被观察到与透明质酸和 RNA 相互作用。这些发现表明 C1QBP 具有线粒体和线粒体外的功能。许多伴侣蛋白的 C1QBP 结合位点位于这些分子的碱性和固有无序区域内,这与 C1QBP 作为分子伴侣的假设一致。在包括乳腺癌在内的各种人类癌症中,C1QBP 的表达升高。此外,基于使用癌细胞系和异种移植模型的功能丧失和功能获得研究,C1QBP 已被牵连到癌细胞的发展、进展和转移中。因此,C1QBP 可能是乳腺癌治疗的一个分子靶标。使用抗体、肿瘤归巢肽(如 LyP-1)和针对 C1QBP 的小分子的研究值得进一步研究,因为 C1QBP 是一个潜在的治疗靶标。

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