TFF-1 Functions to Suppress Multiple Phenotypes Associated with Lung Cancer Progression

Minegishi, Kentaro; Dobashi, Yoh; Tsubochi, Hiroyoshi; Hagiwara, Koichi; Ishibashi, Yuko; Nomura, Sachiyo; Nakamura, Ritsuko; Ohmoto, Yasukazu; Endo, Shunsuke

doi:10.2147/ott.s322697

Cited by 6 publications

(2 citation statements)

References 43 publications

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“…In cancer cell lines, exogenous TFF1 consistently reduced cell proliferation by delaying the G1 to S phase transition in human colonic and gastric carcinoma cells (29). Similarly, in a previous study, it was shown that TFF1 can suppress cell proliferation, survival, migration and invasion in lung carcinoma cells (30). Notably, the expression of TFF1 is also predictive of improved survival time for patients with breast cancer (27,31).…”

Section: Diagnostic Utility Of Trefoil Factor Families For the Early ...mentioning

confidence: 55%

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression

et al. 2023

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Trefoil factors (TFFs) are upregulated in numerous types of cancer, including those of the breast, the colon, the lung and the pancreas, suggesting their potential utility as biomarkers for screening. In the present study, the clinical relevance of serum or urinary TFFs as biomarkers were comprehensively evaluated and the correlation with TFF expression levels in lung cancer tissue was examined. Serum and urine were collected from 199 patients with lung cancer and 198 healthy individuals. Concentrations of serum and urinary TFF1, TFF2 and TFF3 were measured using ELISA and the potential of TFF levels to discriminate between cancer and non-cancer samples was evaluated. In 100 of the cancer cases, expression of TFF1-3 was analyzed using immunohistochemical staining of paraffin sections. Furthermore, the relationship between TFF levels and clinicopathological factors among these cancer cases was analyzed using immunohistochemistry of tissue specimens, quantified and statistically analyzed. While serum levels of all TFFs measured using ELISA were significantly higher in patients with lung cancer compared with those in healthy individuals, urinary TFFs were lower. Areas under the curve (AUC) of the receiver operating characteristic curves for serum/urinary TFF1, TFF2 and TFF3 were 0.709/0.594, 0.722/0.501 and 0.663/0.665, respectively. Furthermore, the combination of serum TFF1, TFF2, TFF3 and urinary TFF1 and TFF3 demonstrated the highest AUC (0.826). In the clinicopathological analysis, serum TFF1 was higher in the early pathological T-stage (pTis/1/2) compared with the later stage (pT3/4) and TFF2 was higher in the pN0/1 than the pN2 group. With regards to the histological types, urinary TFF1 was higher in squamous cell carcinoma than adenocarcinoma (AC), but TFF2 tended to be higher in AC. Using immunohistochemical analysis, although TFF1 and TFF3 expression showed positive correlation with serum concentrations, TFF2 was inversely correlated. In conclusion, serum and urinary TFF levels are promising predictive biomarkers, and their measurements provide a useful in vivo and non-invasive diagnostic screening tool. In particular, TFF1 and TFF3 could be surrogate markers of clinicopathological profiles of human lung cancer.

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Section: Diagnostic Utility Of Trefoil Factor Families For the Early ...mentioning

confidence: 55%

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression

et al. 2023

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“…3b ). Immunofluorescence experiments demonstrated that N protein (in green) was expressed and co-localized with the lung epithelial cell marker TFF-1 43 (in blue) in the lung organoids infected with Lentivirus-N (Supplementary Fig. 3c ).…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication

潘畔

Lei

et al. 2023

Sig Transduct Target Ther

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Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

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Urinary biomarkers analysis as a diagnostic tool for early detection of pancreatic adenocarcinoma: Molecular quantification approach

Samir,

El-Ashry,

Soliman

et al. 2024

Computational Biology and Chemistry

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TFF-1 Functions to Suppress Multiple Phenotypes Associated with Lung Cancer Progression

Cited by 6 publications

References 43 publications

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression

SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication

Urinary biomarkers analysis as a diagnostic tool for early detection of pancreatic adenocarcinoma: Molecular quantification approach

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