SNAIL1: Linking Tumor Metastasis to Immune Evasion

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.

Tumor-associated macrophage-derived chemokine CCL5 facilitates the progression and immunosuppressive tumor microenvironment of clear cell renal cell carcinoma

“…Increasing evidence suggests that the malignant behaviors and treatment resistance of cancers are heavily governed by the crosstalk between the TME and tumor cells 28 . Chemokines are crucial in modulating the activity and tolerance status of tumors, as well as the abundance and cellular differentiation of TILs involved in pro-and anti-tumorigenic immune activities [29][30][31][32] . Previous studies found high CCL5 expression in PBRM1 MUT ccRCC patients that exhibited poor clinical outcomes and increased mast cell infiltration 33 .…”

Role and mechanism of miR-211 in human cancer

“…SNAI1 is a zinc finger transcription factor and functions as a driver of cancer progression [97]. Numerous studies have shown that Snail1 is a crucial inducer of EMT and plays a vital role in tumor metastasis [98].…”

USP41 Enhances Epithelial–Mesenchymal Transition of Breast Cancer Cells through Snail Stabilization

“…Above all, Snail is modulated by various signal pathways at the transcriptional and post-translational levels [ 3 , 4 ]. Snail is degraded by the E3 ligase-dependent ubiquitin proteasome system [ 5 ]. Zhou et al previously identified that β-TrCP1 ubiquitinates Snail through its phosphorylation by GSK-3β [ 6 ].…”