Trefoil factor family (TFF) peptides and cancer progression

Emami, Shahin; Rodrigues, Sylvie; Rodrigue, Christelle M; Floch, Nathalie Le; Rivat, Christine; Attoub, Samir; Bruyneel, Erik; Gespach, Christian

doi:10.1016/j.peptides.2003.10.019

Cited by 114 publications

(81 citation statements)

References 165 publications

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“…Recent studies indicate that TFFs exert dual roles during normal development and malignancies associated with the digestive tract, especially inflammatory processes and cancer progression (Emami et al, 2004;Dhar et al, 2005). During transient injury of the mucosa, TFFs display protective roles on mucosal repair and inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Trefoil factors TFF1 (formerly designated pS2), TFF2 (Spasmolytic Polypeptide), and TFF3 (intestinal trefoil factor) are 7-12 kDa protease-resistant proteins mainly secreted by mucus-secreting cells in the gastrointestinal tract (reviewed in Emami et al, 2004). TFFs are efficient motogenic agents with beneficial effects on the gastrointestinal epithelia, promoting wound healing and mucosal restitution after local injury.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, TFF1 is a candidate gastric-specific tumor suppressor to protect the mucosa against acid, digestive enzymes and pathogens, such as Helicobacter pylori (Rio et al, 1988;Lefebvre et al, 1996;Van De Bovenkamp et al, 2005). In contrast, TFF1 is absent in normal colon but is induced at high levels in Crohn disease and colorectal cancers (Emami et al, 2004). Recent studies incriminate TFF1 and other TFFs in the neoplastic progression of the digestive system, according to their scattering, proinvasive and proangiogenic activities in vitro and in vivo (Emami et al, 2001;Rodrigues et al, 2001Rodrigues et al, , 2003bRivat et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

et al. 2006

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“…In the current literature, TFF peptides are discussed as tumor suppressors and potential tumor progression or oncogenic factors [14]. On the one hand, TFF peptides are overexpressed in several human solid tumors [15,16,17]. TFF3 overexpression is frequently observed in human cancers e.g.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

Philippeit¹,

Busch²,

Dünker³

2014

Cell Physiol Biochem

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Background: Recent studies demonstrated that epigenetic mechanisms are involved in the regulation of trefoil factor family (TFF) peptide expression in cancer. In human tissues with endogenous TFF1, TFF2 or TFF3 gene expression, the corresponding promoter is unmethylated and in organs without TFF expression, the promoter of the three genes is highly methylated. Methods: Retinoblastoma (Rb) cell lines were treated with the DNA methyltransferase inhibitor 5-Aza-2`deoxycytidine (5-Aza-dC), the histone deacetylase inhibitor 4-Phenylbutyric acid (PBA) or both and analyzed for changes (i) in TFF mRNA expression by Real-time PCR and (ii) in the methylation status of the TFF promoters by genomic bisulfite sequencing. Results: The degree of promoter methylation correlates with endogenous TFF expression in the retinoblastoma cell lines analyzed. Nearly all Rb cell lines exhibiting high endogenous TFF1 expression displayed low methylation of the CpGs in the corresponding promoter region. Low expression of TFF3 in Rb cell lines is linked with high density methylation of the TFF3 promoter. 5-Aza-dC treatment induced TFF1 and TFF3 expression in nearly all cell lines investigated and combined treatment with PBA further increased this effect. The number of methylated CpG dinucleotides of the TFF promoter is clearly reduced upon treatment with 5-Aza-dC and combined treatment with PBA further extended the degree of demethylation. Conclusion: Our data clearly show that the expression of TFF3 in retinoblastoma cell lines is epigenetically regulated, whereas the level of TFF1 and TFF2 seems to be regulated by other or additional mechanisms.

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“…Despite the absence of an identified cell surface receptor for TFF2, there is nevertheless clear evidence that TFF2 and TFF3 rapidly activate signal transduction pathways (17,18). TFF3 prevents cell death via activation of the serine/threonine kinase AKT in colon cancer cell lines (19).…”

mentioning

confidence: 99%

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

Dubeykovskaya

Dubeykovskiy

Solal-Cohen

et al. 2009

Journal of Biological Chemistry

101

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The secreted trefoil factor family 2 (TFF2) protein contributes to the protection of the gastrointestinal mucosa from injury by strengthening and stabilizing mucin gels, stimulating epithelial restitution, and restraining the associated inflammation. Although trefoil factors have been shown to activate signaling pathways, no cell surface receptor has been directly linked to trefoil peptide signaling. Here we demonstrate the ability of TFF2 peptide to activate signaling via the CXCR4 chemokine receptor in cancer cell lines. We found that both mouse and human TFF2 proteins (at ϳ0.5 M) activate Ca 2؉ signaling in lymphoblastic Jurkat cells that could be abrogated by receptor desensitization (with SDF-1␣) or pretreatment with the specific antagonist AMD3100 or an anti-CXCR4 antibody. TFF2 pretreatment of Jurkat cells decreased Ca 2؉ rise and chemotactic response to SDF-1␣. In addition, the CXCR4-negative gastric epithelial cell line AGS became highly responsive to TFF2 treatment upon expression of the CXCR4 receptor. TFF2-induced activation of mitogen-activated protein kinases in gastric and pancreatic cancer cells, KATO III and AsPC-1, respectively, was also dependent on the presence of the CXCR4 receptor. Finally we demonstrate a distinct proliferative effect of TFF2 protein on an AGS gastric cancer cell line that expresses CXCR4. Overall these data identify CXCR4 as a bona fide signaling receptor for TFF2 and suggest a mechanism through which TFF2 may modulate immune and tumorigenic responses in vivo.

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Trefoil factor family (TFF) peptides and cancer progression

Cited by 114 publications

References 165 publications

Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

Induction of the adenoma-carcinoma progression and Cdc25A-B phosphatases by the trefoil factor TFF1 in human colon epithelial cells

Epigenetic Control of Trefoil Factor Family (TFF) Peptide Expression in Human Retinoblastoma Cell Lines

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

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