scholarly journals Regulation of transforming growth factor-β signalling by SUMOylation and its role in fibrosis

Open Biology ◽  
2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Xinyi Wang ◽  
Ting Liu ◽  
Yifei Huang ◽  
Yifeng Dai ◽  
Hui Lin
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Therapeutic Strategies ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Post Translational Modifications ◽  
Mesenchymal Transition

Fibrosis is an abnormal healing process that only repairs the structure of an organ after injury and does not address damaged functions. The pathogenesis of fibrosis is multifactorial and highly complex; numerous signalling pathways are involved in this process, with the transforming growth factor-β (TGF-β) signalling pathway playing a central role. TGF-β regulates the generation of myofibroblasts and the epithelial–mesenchymal transition by regulating transcription and translation of downstream genes and precisely regulating fibrogenesis. The TGF-β signalling pathway can be modulated by various post-translational modifications, of which SUMOylation has been shown to play a key role. In this review, we focus on the function of SUMOylation in canonical and non-canonical TGF-β signalling and its role in fibrosis, providing promising therapeutic strategies for fibrosis.

scholarly journals Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β

2018 ◽  
Vol 19 (11) ◽  
pp. 3672 ◽  
Author(s):  
Yutaro Tsubakihara ◽  
Aristidis Moustakas
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Basement Membranes ◽  
The Body ◽  
Common Denominator ◽  
Adhesion Forces ◽  
Mesenchymal Transition

Metastasis of tumor cells from primary sites of malignancy to neighboring stromal tissue or distant localities entails in several instances, but not in every case, the epithelial-mesenchymal transition (EMT). EMT weakens the strong adhesion forces between differentiated epithelial cells so that carcinoma cells can achieve solitary or collective motility, which makes the EMT an intuitive mechanism for the initiation of tumor metastasis. EMT initiates after primary oncogenic events lead to secondary secretion of cytokines. The interaction between tumor-secreted cytokines and oncogenic stimuli facilitates EMT progression. A classic case of this mechanism is the cooperation between oncogenic Ras and the transforming growth factor β (TGFβ). The power of TGFβ to mediate EMT during metastasis depends on versatile signaling crosstalk and on the regulation of successive waves of expression of many other cytokines and the progressive remodeling of the extracellular matrix that facilitates motility through basement membranes. Since metastasis involves many organs in the body, whereas EMT affects carcinoma cell differentiation locally, it has frequently been debated whether EMT truly contributes to metastasis. Despite controversies, studies of circulating tumor cells, studies of acquired chemoresistance by metastatic cells, and several (but not all) metastatic animal models, support a link between EMT and metastasis, with TGFβ, often being a common denominator in this link. This article aims at discussing mechanistic cases where TGFβ signaling and EMT facilitate tumor cell dissemination.

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