γ-synuclein and the progression of cancer

The synucleins are a small, soluble, highly conserved group of neuronal proteins that have been implicated in both neurodegenerative diseases and cancer. The synuclein family consists of alpha-, beta-, and gamma-synucleins (gamma-syn). They are a natively unfolded group of proteins that share sequence homologies and structural properties ( 1, 2). So far, the biological functions of the synucleins are still unclear, but their involvement in neurodegenerative diseases and cancer may provide insights into the pathological processes that result from these two groups of debilitating diseases, and present the possibility to use them as potential targets for early diagnosis and treatment. Recently, elevated levels of gamma-syn proteins have been detected in various types of cancer, especially in advanced stages of the disease. Furthermore, studies to date indicate that overexpression of gamma-syn compromises normal mitotic checkpoint controls, resulting in multinucleation as well as faster cell growth. gamma-Syn has also been shown to promote invasion and metastasis in in vitro assays as well as in animal models. Overexpression of gamma-syn also interferes with drug-induced apoptotic responses. These observations raise questions about the involvement of gamma-syn in the process of tumorigenesis and metastasis, and efforts have already been made to use gamma-syn as a marker for assessing breast cancer progression ( 3). This review will discuss the involvement of gamma-syn in cancer progression, metastasis and its potential as a marker.