TGF- : Duality of Function Between Tumor Prevention and Carcinogenesis

Principe, Daniel R.; Doll, Jennifer A.; Bauer, Jessica; Jung, Barbara; Munshi, Hidayatullah G.; Bartholin, Laurent; Pasche, Boris; Lee, Chung; Grippo, Paul J.

doi:10.1093/jnci/djt369

Cited by 452 publications

(437 citation statements)

References 198 publications

(278 reference statements)

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“…As previously reported, TGF-β induces EMT in various types of cancer cells, increasing their invasion and migration and resulting in enhanced metastasis (22,23,29). The present study demonstrated that MCF-7 and A549 human cancer cells may be induced by TGF-β to undergo a stimulated EMT, reducing E-cadherin expression level in cancer cells and increasing their invasiveness and migration.…”

Section: Discussionsupporting

confidence: 82%

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

et al. 2017

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Abstract. Hispolon (HPL), isolated from Phellinus linteus, has been used to treat various types of pathology, including inflammation, gastroenteric disorders, lymphatic diseases and numerous cancer subtypes. HPL has previously been reported to demonstrate a significant therapeutic efficacy against various types of cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder and gastric cancer cells. However, its potential role in the epithelial-mesenchymal transition (EMT) has not been demonstrated. The present study investigated the effects of HPL on the EMT. Transforming growth factor β (TGF-β) induced enhanced cell migration and invasion, EMT-associated phenotypic changes. In the present study, HPL recovered the reduction of E-cadherin expression level in TGF-β treated cancer cells, which was regulated by the expression of Snail and Twist. HPL downregulated Snail and Twist, an effect that was enhanced by TGF-β. These findings provide novel evidence that HPL suppresses cancer cell migration and invasion by inhibiting EMT. Therefore, HPL may be a potent anticancer agent, inhibiting metastasis.

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Section: Discussionsupporting

confidence: 82%

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

et al. 2017

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“…57 Thus, we have the following equations describing the dynamics of the two cancer cell populations:…”

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confidence: 99%

Mathematical modelling of cancer invasion: The multiple roles of TGF-β pathway on tumour proliferation and cell adhesion

Bitsouni

Chaplain

Eftimie

2017

Math. Models Methods Appl. Sci.

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In this paper, we develop a non-local mathematical model describing cancer cell invasion and movement as a result of integrin-controlled cell-cell adhesion and cell-matrix adhesion, and transforming growth factor-beta (TGF-β) effect on cell proliferation and adhesion, for two cancer cell populations with different levels of mutation. The model consists of partial integro-differential equations describing the dynamics of two cancer cell populations, coupled with ordinary differential equations describing the extracellular matrix (ECM) degradation and the production and decay of integrins, and with a parabolic PDE governing the evolution of TGF-β concentration. We prove the global This is an Open Access article published by World Scientific Publishing Company. It is distributed under the terms of the Creative Commons Attribution 4.0 (CC-BY) License. Further distribution of this work is permitted, provided the original work is properly cited.

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“…9 Among these ECM proteins, the transforming growth factor-β (TGF-β) acts in PDA as a potent tumor suppressor and tumor promoter in a contextdependent manner. 10,11 In PDA, TGF-β impacts are driven by Sma and Mad-related protein (SMAD)2/3/4 pathway activation/ inactivation as well as by SMAD-independent pathways, that is, phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway, JNK/p38 non-Smad pathway or mitogen-activated protein kinase (MAPK) pathway. 12,13 Overall, PDA studies support the notion that disabling TGF-β/Smad4 signaling pathway may be a critical event in pancreatic cancer progression, and open up a specific route toward the design of biomarkers as well as adjuvant therapies for this pathology.…”

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confidence: 99%

TAp73 loss favors Smad-independent TGF-β signaling that drives EMT in pancreatic ductal adenocarcinoma

et al. 2016

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Advances made in pancreatic cancer therapy have been far from sufficient and have allowed only a slight improvement in global survival of patients with pancreatic ductal adenocarcinoma (PDA). Recent progresses in chemotherapy have offered some hope for an otherwise gloomy outlook, however, only a limited number of patients are eligible because of important cytotoxicity. In this context, enhancing our knowledge on PDA initiation and evolution is crucial to highlight certain weaknesses on which to specifically target therapy. We found that loss of transcriptionally active p73 (TAp73), a p53 family member, impacted PDA development. In two relevant and specific engineered pancreatic cancer mouse models, we observed that TAp73 deficiency reduced survival and enhanced epithelial-to-mesenchymal transition (EMT). Through proteomic analysis of conditioned media from TAp73 wild-type (WT) and deficient pancreatic tumor cells, we identified a secreted protein, biglycan (BGN), which is necessary and sufficient to mediate this pro-EMT effect. Interestingly, BGN is modulated by and modulates the transforming growth factor-β (TGF-β) pathway, a key regulator of the EMT process. We further examined this link and revealed that TAp73 impacts the TGF-β pathway by direct regulation of BGN expression and Sma and Mad-related proteins (SMADs) expression/ activity. Absence of TAp73 leads to activation of TGF-β signaling through a SMAD-independent pathway, favoring oncogenic TGF-β effects and EMT. Altogether, our data highlight the implication of TAp73 in the aggressiveness of pancreatic carcinogenesis through modulation of the TGF-β signaling. By suggesting TAp73 as a predictive marker for response to TGF-β inhibitors, our study could improve the classification of PDA patients with a view to offering combined therapy involving TGF-β inhibitors.

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TGF- : Duality of Function Between Tumor Prevention and Carcinogenesis

Cited by 452 publications

References 198 publications

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

Hispolon as an inhibitor of TGF-β-induced epithelial-mesenchymal transition in human epithelial cancer cells by co-regulation of TGF-β-Snail/Twist axis

Mathematical modelling of cancer invasion: The multiple roles of TGF-β pathway on tumour proliferation and cell adhesion

TAp73 loss favors Smad-independent TGF-β signaling that drives EMT in pancreatic ductal adenocarcinoma

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