Abstract
The transcription factor Snail1, a key inducer of epithelial-mesenchymal transition (EMT), plays a critical role in tumor metastasis. Its stability is strictly controlled by multiple intracellular signal transduction pathways and the ubiquitin-proteasome system (UPS). Increasing evidence indicates that methylation and acetylation of Snail1 also affects tumor metastasis. More importantly, Snail1 is involved in tumor immunosuppression by inducing chemokines and immunosuppressive cells into the tumor microenvironment (TME). In addition, some immune checkpoints potentiate Snail1 expression, such as programmed death ligand 1 (PD-L1) and T cell immunoglobulin 3 (TIM-3). This mini review highlights the pathways and molecules involved in maintenance of Snail1 level and the significance of Snail1 in tumor immune evasion. Due to the crucial role of EMT in tumor metastasis and tumor immunosuppression, comprehensive understanding of Snail1 function may contribute to the development of novel therapeutics for cancer.
Highlights
Metastasis is one of the most prominent features of malignant tumors and is the leading cause of death in tumor patients [1]
It was reported that immune checkpoint molecules such as programmed death ligand 1 (PD-L1) are involved in epithelial-mesenchymal transition (EMT) regulation, while EMT can induce immunosuppression and immune evasion in tumors [3]
It is well known that Akt can phosphorylate and inhibit GSK-3b activity, subsequently suppressing the GSK-3b-mediated phosphorylation of Snail1 and facilitating its stabilization and nuclear localization, which promotes EMT widely presenting in a variety of tumors [31,32,33,34,35,36]
Summary
Metastasis is one of the most prominent features of malignant tumors and is the leading cause of death in tumor patients [1]. As a transcriptional repressor, is implicated in the regulation of other tumor metastasis suppressors, such as the epithelial marker E-cadherin [11]. The expression of Snail is regulated by many signaling pathways both at the transcriptional and protein level [16, 17] (Figure 1B). It is well known that Akt can phosphorylate and inhibit GSK-3b activity, subsequently suppressing the GSK-3b-mediated phosphorylation of Snail and facilitating its stabilization and nuclear localization, which promotes EMT widely presenting in a variety of tumors [31,32,33,34,35,36]. Some studies indicate TGF-b regulates Snail expression via the Akt/GSK-3b signaling pathway in osteosarcoma and ovarian clear cell carcinoma [41, 42]
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