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

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.