The complement component 1, q subcomponent binding protein (C1QBP/p32/HABP1) is an acidic protein that binds the complement component C1q and is designated as the gC1q receptor. Its mature form contains between 74 and 282 amino acid residues generated by the removal of the N-terminal mitochondria targeting sequence (1 to 73 amino acid residues) during post-translational processing. It is mainly distributed in mitochondria, but it can also be detected in the cytosol, cell surface, and nucleus of different cells. Complement component C1QBP has been reported to be overexpressed in thyroid, colon, pancreatic, gastric, and lung adenocarcinomas. Several studies have proposed different roles of complement component C1QBP in tumorigenesis. Fogal et al. suggested that complement component C1QBP was required in order for tumor cells to maintain oxidative phosphorylation, and a cell surface receptor form of complement component C1QBP was reported to regulate lamellipodia formation in cancer cells.
Metastasis is the leading cause of death among cancer patients. Chemotaxis, a chemical-induced directional migration of cells, regulates metastasis at various stages, including epidermal growth factor (EGF)-induced breast cancer cell intravasation into circulation and chemokine ligand 12-mediated extravasation to the secondary organs. Ghosh et al. reported that complement component C1QBP overexpression was confined to metastatic islands during the onset of metastasis, which implied its potential role in regulating tumor metastasis.
In addition, complement C1QBP was required for breast cancer metastasis in a severe combined immunodeficiency mouse model. Furthermore, complement C1QBP was observed to be overexpressed in breast cancer tissues, and its expression level was closely linked with distant metastasis and TNM stages. In summary, complement C1QBP was identified as a novel regulator of cancer metastasis that may serve as a therapeutic target for breast cancer treatment.
1. Zhang X, et al. (2013). Interactome analysis reveals that C1QBP (complement component 1, q subcomponent binding protein) is associated with cancer cell chemotaxis and metastasis. Molecular & Cellular Proteomics, 12(11), 3199-3209.
2. Ghebrehiwet B, et al. (1994). Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. The Journal of experimental medicine, 179(6), 1809-1821.