Role and function of plakophilin 3 in cancer progression and skin disease

Plakophilin 3 (PKP3), a component of desmosome, is aberrantly expressed in many kinds of human diseases, especially in cancers. Through direct interaction, PKP3 binds with a series of desmosomal proteins, such as desmoglein, desmocollin, plakoglobin, and desmoplakin, to initiate desmosome aggregation, then promotes its stability. As PKP3 is mostly expressed in the skin, loss of PKP3 promotes the development of several skin diseases, such as paraneoplastic pemphigus, pemphigus vulgaris, and hypertrophic scar. Moreover, accumulated clinical data indicate that PKP3 dysregulates in diverse cancers, including breast, ovarian, colon, and lung cancers. Numerous lines of evidence have shown that PKP3 plays important roles in multiple cellular processes during cancer progression, including metastasis, invasion, tumor formation, autophagy, and proliferation. This review examines the diverse functions of PKP3 in regulating tumor formation and development in various types of cancers and summarizes its detailed mechanisms in the occurrence of skin diseases.