TFF-1 Functions to Suppress Multiple Phenotypes Associated with Lung Cancer Progression.
TFF-1
apoptosis
growth inhibition
invasion
lung carcinoma cells
migration
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2021
2021
Historique:
received:
10
06
2021
accepted:
24
08
2021
entrez:
17
9
2021
pubmed:
18
9
2021
medline:
18
9
2021
Statut:
epublish
Résumé
Trefoil Factor (TFF) is a member of a protein family comprised of three isoforms, of which TFF-1 exhibits antithetical functions; promotion or suppression of cell proliferation, survival and invasion, depending on the cancer type. However, the pathobiological function of TFF-1 in lung carcinoma has been still unclear. We examined the expression and secretion of TFF-1 using cultured human lung carcinoma cells by immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR analyses. The effects of TFF-1 on various phenotypes were analyzed in two cell lines, including those transfected with cDNA encoding TFF-1. Cell proliferation and death were examined by hemocytometer cell counting and by colorimetric viability/cytotoxicity assay. Cell cycle profile, migration and invasion were also examined by flow cytometry, wound healing assay and Matrigel Transwell assay, respectively. The effect of TFF-1 overexpression was confirmed by additional transfection of TFF-1-specific siRNA. Endogenous TFF-1 protein expression and secretion into the media were observed exclusively in adenocarcinoma-derived cell lines. Forced overexpression of TFF-1 drove cell cycle transition, while the proliferation decreased by 19% to 25% due to increased cell death. This cell death was predominantly caused by apoptosis, as assessed by the activation of caspase 3/7. Cell migration was also suppressed by 71% to 82% in TFF-1-transfected cells. The suppressive effect of TFF-1 on proliferation and migration was restored by transfection of TFF-1 siRNA. Moreover, invasion was also suppressed to 77% to 83% in TFF-1-transfected cells. These findings reveal that TFF-1 functions as a suppressor of cancer proliferation by induction of apoptosis, cell migration and invasion and thus may provide a synergistic target for potential treatment strategies for human lung carcinoma.
Identifiants
pubmed: 34531663
doi: 10.2147/OTT.S322697
pii: 322697
pmc: PMC8439977
doi:
Types de publication
Journal Article
Langues
eng
Pagination
4761-4777Informations de copyright
© 2021 Minegishi et al.
Déclaration de conflit d'intérêts
The authors report no editorial or financial conflicts of interest in this work.
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