An approach to p32/gC1qR/HABP1: a multifunctional protein with an essential role in cancer.

P32/gC1qR/HABP1 is a doughnut-shaped acidic protein, highly conserved in eukaryote evolution and ubiquitous in the organism. Although its canonical subcellular localization is the mitochondria, p32 can also be found in the cytosol, nucleus, cytoplasmic membrane, and it can be secreted. Therefore, it is considered a multicompartmental protein. P32 can interact with many physiologically divergent ligands in each subcellular location and modulate their functions. The main ligands are C1q, hyaluronic acid, calreticulin, CD44, integrins, PKC, splicing factor ASF/SF2, and several microbial proteins. Among the functions in which p32 participates are mitochondrial metabolism and dynamics, apoptosis, splicing, immune response, inflammation, and modulates several cell signaling pathways. Notably, p32 is overexpressed in a significant number of epithelial tumors, where its expression level negatively correlates with patient survival. Several studies of gain and/or loss of function in cancer cells have demonstrated that p32 is a promoter of malignant hallmarks such as proliferation, cell survival, chemoresistance, angiogenesis, immunoregulation, migration, invasion, and metastasis. All of this strongly suggests that p32 is a potential diagnostic molecule and therapeutic target in cancer. Indeed, preclinical advances have been made in developing therapeutic strategies using p32 as a target. They include tumor homing peptides, monoclonal antibodies, an intracellular inhibitor, a p32 peptide vaccine, and p32 CAR T cells. These advances are promising and will allow soon to include p32 as part of targeted cancer therapies.