- Post-translational control plays a crucial role in modulating the dynamics and reversibility of epithelial-to-mesenchymal transition (EMT) by altering the stability, localization, and activity of EMT-related proteins after they are synthesized.
- These modifications include phosphorylation, ubiquitination, sumoylation, acetylation, and glycosylation, which fine-tune the function of key EMT markers and transcription factors without altering gene expression directly.
- For example, Snail, a key EMT-inducing transcription factor, is subject to phosphorylation by GSK-3β, which leads to its nuclear export and degradation via ubiquitination by E3 ligases such as β-TrCP. This post-translational regulation controls the duration and extent of Snail’s transcriptional repression of epithelial markers like E-cadherin.
- Similarly, β-catenin, which plays dual roles in cell adhesion and Wnt signaling, undergoes phosphorylation-dependent degradation, but when stabilized, it can translocate to the nucleus and promote EMT by activating mesenchymal gene expression.
- In addition, modifications of cytoskeletal proteins such as vimentin, or ECM components like fibronectin, influence cell morphology, adhesion, and motility, which are critical for EMT progression.
- Post-translational regulation adds a rapid and reversible layer of control, allowing cells to respond to microenvironmental cues such as growth factors, mechanical stress, or hypoxia. This is especially important in cancer, where EMT is often partial or transient and requires tight temporal control. Thus, targeting post-translational regulators—such as kinases, phosphatases, or ubiquitin ligases—represents a promising approach in EMT-related therapeutics for diseases like cancer, fibrosis, and chronic inflammation.
