Unpacking the Tumor Protein D52-like Family: Roles in Intracellular Trafficking and Cancer Progression

There is growing evidence that dysregulation of vesicle-mediated intracellular trafficking pathways leads to the development of various diseases, including cancer. Cancer exploits the intracellular trafficking pathways to modulate the protein flow, alter cell surface protein expression, and drive the hallmarks of cancer progression, such as sustained proliferation signaling and evading immune surveillance. As such, there is increasing interest in understanding the proteins that regulate these processes to better understand cancer biology and to identify novel ways to hinder disease progression. A group of small proteins, known as the Tumor Protein D52 (TPD52)-like family, has been identified and is increasingly recognized for its roles in intracellular trafficking within cancer cells. This family consists of four members: TPD52, TPD53, TPD54, and TPD55. Herein, we review the current literature on the TPD52-like family in cancer and detail the current known cellular functions (e.g., intracellular trafficking roles, lipid biogenesis, cell proliferation, and cell cycle regulation). Overexpression of family members, notably TPD52 and TPD54, has been heavily implicated in tumorigenic roles such as cell migration, invasion, proliferation, and protein-protein interactions. Additionally, there is mounting evidence that this family also has isoform-specific and/or tissue-specific functions, which is of clinical interest. A better understanding of the mechanistic actions of this protein family holds the promise of identifying novel therapeutic targets that exploit the broader multi-target nature of intracellular trafficking regulators to disrupt oncogenic processes.