» Articles » PMID: 31275381

Roles of the Phosphorylation of Transcriptional Factors in Epithelial-Mesenchymal Transition

Overview
Journal J Oncol
Specialty Oncology
Date 2019 Jul 6
PMID 31275381
Citations 41
Authors
Affiliations
Soon will be listed here.
Abstract

Epithelial-to-mesenchymal transition (EMT) is the first step in the development of the invasive and migratory properties of cancer metastasis. Since the transcriptional reprogramming of a number of genes occurs in EMT, the regulation of EMT transcription factors has been intensively investigated. EMT transcriptional factors are commonly classified by the direct or indirect repression of E-cadherin because one of hallmarks of EMT is the loss of E-cadherin. This facilitates the expression of genes for EMT, tumor invasion, and metastasis. The posttranslational modification of EMT transcriptional factors, such as Snail and Slug, directly regulates their functions, including their stability, nuclear localization, protein-protein interaction, and ubiquitination for the promotion or termination of EMT at the specific points. Here, we discuss how posttranslational modifications regulate gene expression in a dynamic and reversible manner by modifying upstream signaling pathways, focusing in particular on the posttranslational modifications of Snail, Slug, ZEB1, ZEB2, and TWIST1. This review demonstrates that EMT transcription factors regulate metastasis through their posttranslational modifications and that the flexibility and reversibility of EMT can be modified by phosphorylation.

Citing Articles

Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.

Seymour L, Nuru N, Johnson K, Gutierrez J, Njoku V, Darie C Molecules. 2025; 30(3).

PMID: 39942749 PMC: 11820228. DOI: 10.3390/molecules30030645.


Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer.

Bruno P, Arshad A, Gogu M, Waterman N, Flack R, Dunn K Life (Basel). 2025; 15(1).

PMID: 39860065 PMC: 11766951. DOI: 10.3390/life15010126.


Bio-Pathological Functions of Posttranslational Modifications of Histological Biomarkers in Breast Cancer.

Neagu A, Josan C, Jayaweera T, Morrissiey H, Johnson K, Darie C Molecules. 2024; 29(17).

PMID: 39275004 PMC: 11397409. DOI: 10.3390/molecules29174156.


Metformin Attenuates Partial Epithelial-Mesenchymal Transition in Salivary Gland Inflammation via PI3K/Akt/GSK3β/Snail Signaling Axis.

Peng B, Wang L, Pan S, Kang J, Wei L, Li B Inflammation. 2024; .

PMID: 39269669 DOI: 10.1007/s10753-024-02142-y.


Amphiregulin Downregulates E-cadherin Expression by Activating YAP/Egr-1/Slug Signaling in SKOV3 Human Ovarian Cancer Cells.

Jia Q, Wang H, Bi B, Han X, Jia Y, Zhang L Reprod Sci. 2024; 32(2):404-416.

PMID: 39138796 DOI: 10.1007/s43032-024-01673-x.


References
1.
Cano A, Perez-Moreno M, Rodrigo I, Locascio A, Blanco M, del Barrio M . The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol. 2000; 2(2):76-83. DOI: 10.1038/35000025. View

2.
Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J . The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000; 2(2):84-9. DOI: 10.1038/35000034. View

3.
Hemavathy K, Guru S, Harris J, Chen J, Ip Y . Human Slug is a repressor that localizes to sites of active transcription. Mol Cell Biol. 2000; 20(14):5087-95. PMC: 85958. DOI: 10.1128/MCB.20.14.5087-5095.2000. View

4.
Hemavathy K, Ashraf S, Ip Y . Snail/slug family of repressors: slowly going into the fast lane of development and cancer. Gene. 2000; 257(1):1-12. DOI: 10.1016/s0378-1119(00)00371-1. View

5.
Perez-Moreno M, Locascio A, Rodrigo I, Dhondt G, Portillo F, Nieto M . A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J Biol Chem. 2001; 276(29):27424-31. DOI: 10.1074/jbc.M100827200. View