ALDH1B1 Is Crucial for Colon Tumorigenesis by Modulating Wnt/β-Catenin, Notch and PI3K/Akt Signaling Pathways.
作者： Surendra Singh , John Arcaroli , Ying Chen , David C. Thompson , Wells Messersmith
DOI: 10.1371/JOURNAL.PONE.0121648
关键词: Carcinogenesis 、 Protein kinase B 、 Notch signaling pathway 、 PI3K/AKT/mTOR pathway 、 Signal transduction 、 Cell biology 、 Wnt signaling pathway 、 Transcription factor 、 Catenin 、 Biology
摘要: In the normal human colon, aldehyde dehydrogenase 1B1 (ALDH1B1) is expressed only at crypt base, along with stem cells. It also highly in colonic adenocarcinomas. This pattern of expression corresponds closely to that observed for Wnt/β-catenin signaling activity. The present study examines role ALDH1B1 colon tumorigenesis and signalling pathways mediating its effects. a 3-dimensional spheroid growth model nude mouse xenograft tumor model, shRNA-induced suppression decreased number size spheroids formed vitro tumors vivo by SW 480 Six binding elements transcription factor (T-cell factor/ lymphoid enhancing factor) were identified gene promoter (3 kb) but shown dual luciferase reporter assay not be necessary mRNA adenocarcinoma cell lines. We examined Wnt-reporter activity protein/mRNA Wnt, Notch PI3K/Akt pathways. Wnt/β-catenin, PI3K/Akt-signaling down-regulated cells which had been suppressed. summary, our data demonstrate may promote cancer modulating Selective targeting represent novel means prevent or treat cancer.
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