γ-Synuclein as a Cancer Biomarker: Viewpoint and New Approaches
Department of Neurology, Kansas University Medical Center, Kansas City, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Synucleinopathies are complex diseases that progress through several steps, and increasing evidence suggests that an early diagnosis might significantly increase the efficacy of the treatment. A member of the synuclein family, α-synuclein is associated with neurodegenerative diseases, whereas another member, γ-synuclein is implicated predominantly in various forms of cancer. Synucleins can be physiologically secreted to the extracellular space. Accumulating evidence suggests that secretion and cell-to-cell trafficking of both α- and γ-synuclein may explain the typical patterns of disease progression, however, the molecular mechanisms controlling spreading of pathology are still elusive. Several mechanisms may explain the presence of synucleins in extracellular liquids, including passive diffusion, exosome-mediated secretion, unconventional secretion through exophagy, etc. Analysis of extracellular synucleins in body fluids may reveal the first steps of the disease, become an important diagnostic tool and demonstrate the efficiency of the treatment. γ-Synuclein is secreted from tumor cells and elevated levels of γ-synuclein have been detected in various types of cancer, especially in advanced stages of the disease. Urinary analysis of γ-synuclein is proved to be important for early diagnosis of at least one type of oncologic diseases, bladder cancer. Dynamic intracellular localization of γ-synuclein and its ability to migrate between cells suggest that this analysis may have diagnostic and prognostic value for other types of cancer.
Keywords: synucleins, cancer diagnostics, protein secretion, urine biomarkers.