γ‐Synuclein and the progression of cancer

Abstract

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. 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. This review will discuss the involvement of gamma-syn in cancer progression, metastasis and its potential as a marker.

Expression of α-, β- and γ-synuclein in colorectal cancer, and potential clinical significance in progression of the disease

“…These repeats result in the formation of conserved amphipathic A2-helices also characteristic of apolipoproteins, which mediate reversible binding to phospholipid membranes. This property supports the role of synucleins in vesicular release at presynaptic nerve terminals (1)(2)(3)(4). Although their normal cellular functions have not been clearly defined, synucleins have attracted considerable attention due to their involvement in neurodegenerative diseases.…”

Expression of γ-synuclein in colorectal cancer tissues and its role on colorectal cancer cell line HCT116

“…γ-synuclein belongs to the synuclein protein family, consisting of α-, β-, and γ-synuclein, which are abundantly expressed in nervous tissues [9] . Although there has been a report that showed down-regulation of γ-synuclein in human ESCC, more studies support the statement of over-expression of γ-synuclein in more types of cancer [14,15,[20][21][22] .…”

“…γ-synuclein gene [also referred to as breast carcinoma specific gene 1 (BCSG1)] initially was cloned from infiltrating breast carcinoma cells by using the expressed sequence tag-based differential cDNA sequencing approach [8] . γ-synuclein maps to chromosome region 10q23, and is composed of five exons and transcribed into an mRNA of about 1 kb, coding 127 amino acids [9] . γ-synuclein expression is usually highly tissue-specific and restricted to brain tissue and presynaptic terminals [2] .…”

Recapitulation of zebrafish sncga expression pattern and labeling the habenular complex in transgenic zebrafish using green fluorescent protein reporter gene

“…In contrast, ␤-synuclein could inhibit ␣-synuclein aggregation, suggesting a possible role as an antiparkinsonian factor (Hashimoto et al, 2001;Bertoncini et al, 2007;Tsigelny et al, 2007). The ␥-synuclein is also known as BCSG-1 (breast cancer-specific gene 1; Ji et al, 1997) and has been shown to associate with cancer progression and may be used as a tumor marker (Jia et al, 1999;Iwaki et al, 2004;Li et al, 2004;Ahmad et al, 2007).…”