scholarly journals TGF-β Signaling and Resistance to Cancer Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Maoduo Zhang ◽  
Ying Yi Zhang ◽  
Yongze Chen ◽  
Jia Wang ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Multiple Drug Resistance ◽  
Transforming Growth Factor Β ◽  
Multiple Drug ◽  
Cancer Resistance ◽  
Mesenchymal Transition ◽  
Key Factor ◽  
Cancer Multiple

The transforming growth factor β (TGF-β) pathway, which is well studied for its ability to inhibit cell proliferation in early stages of tumorigenesis while promoting epithelial-mesenchymal transition and invasion in advanced cancer, is considered to act as a double-edged sword in cancer. Multiple inhibitors have been developed to target TGF-β signaling, but results from clinical trials were inconsistent, suggesting that the functions of TGF-β in human cancers are not yet fully explored. Multiple drug resistance is a major challenge in cancer therapy; emerging evidence indicates that TGF-β signaling may be a key factor in cancer resistance to chemotherapy, targeted therapy and immunotherapy. Finally, combining anti-TGF-β therapy with other cancer therapy is an attractive venue to be explored for the treatment of therapy-resistant cancer.

scholarly journals N6-Methyladenosine Regulates the Expression and Secretion of TGFβ1 to Affect the Epithelial–Mesenchymal Transition of Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 296 ◽  
Author(s):  
Jiexin Li ◽  
Feng Chen ◽  
Yanxi Peng ◽  
Ziyan Lv ◽  
Xinyao Lin ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Transforming Growth Factor Β ◽  
Dimer Formation ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Key Factor ◽  
The Relationship

N6-methyladenosine (m6A) is the most abundant modification on eukaryotic mRNA, which regulates all steps of the mRNA life cycle. An increasing number of studies have shown that m6A methylation plays essential roles in tumor development. However, the relationship between m6A and the progression of cancers remains to be explored. Here, we reported that transforming growth factor-β (TGFβ1)-induced epithelial–mesenchymal transition (EMT) was inhibited in methyltransferase-like 3 (METTL3) knockdown (Mettl3Mut/−) cells. The expression of TGFβ1 was up-regulated, while self-stimulated expression of TGFβ1 was suppressed in Mettl3Mut/− cells. We further revealed that m6A promoted TGFB1 mRNA decay, but impaired TGFB1 translation progress. Besides this, the autocrine of TGFβ1 was disrupted in Mettl3Mut/− cells via interrupting TGFβ1 dimer formation. Lastly, we found that Snail, which was down-regulated in Mettl3Mut/− cells, was a key factor responding to TGFβ1-induced EMT. Together, our research demonstrated that m6A performed multi-functional roles in TGFβ1 expression and EMT modulation, suggesting the critical roles of m6A in cancer progression regulation.

scholarly journals The Molecular Mechanism of Epithelial–Mesenchymal Transition for Breast Carcinogenesis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 476 ◽  
Author(s):  
Chia-Jung Li ◽  
Pei-Yi Chu ◽  
Giou-Teng Yiang ◽  
Meng-Yu Wu
Keyword(s):  
Epithelial Cells ◽  
Tumor Progression ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Inhibition Of Proliferation ◽  
Mesenchymal Transition

The transforming growth factor-β (TGF-β) signaling pathway plays multiple regulatory roles in the tumorigenesis and development of cancer. TGF-β can inhibit the growth and proliferation of epithelial cells and induce apoptosis, thereby playing a role in inhibiting breast cancer. Therefore, the loss of response in epithelial cells that leads to the inhibition of cell proliferation due to TGF-β is a landmark event in tumorigenesis. As tumors progress, TGF-β can promote tumor cell invasion, metastasis, and drug resistance. At present, the above-mentioned role of TGF-β is related to the interaction of multiple signaling pathways in the cell, which can attenuate or abolish the inhibition of proliferation and apoptosis-promoting effects of TGF-β and enhance its promotion of tumor progression. This article focuses on the molecular mechanisms through which TGF-β interacts with multiple intracellular signaling pathways in tumor progression and the effects of these interactions on tumorigenesis.

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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