TIPE1 impairs stemness maintenance in colorectal cancer through directly targeting β-catenin.
Animals
Cell Proliferation
Colon
/ pathology
Colorectal Neoplasms
/ mortality
Down-Regulation
HCT116 Cells
HT29 Cells
Humans
Intracellular Signaling Peptides and Proteins
/ metabolism
Kaplan-Meier Estimate
Male
Mice
Neoplastic Stem Cells
/ pathology
Prognosis
Proteolysis
Tissue Array Analysis
Wnt Signaling Pathway
Xenograft Model Antitumor Assays
beta Catenin
/ metabolism
Journal
Carcinogenesis
ISSN: 1460-2180
Titre abrégé: Carcinogenesis
Pays: England
ID NLM: 8008055
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
09
12
2018
revised:
16
04
2019
accepted:
28
04
2019
pubmed:
22
5
2019
medline:
22
8
2020
entrez:
22
5
2019
Statut:
ppublish
Résumé
TIPE1 (tumor necrosis factor-α-induced protein 8-like 1) contributes to cell death in diverse cancers. However, the expression and biological functions of TIPE1 in colon cancer remain unclear. In the present study, we report that TIPE1 was downregulated in colon cancer tissues and positively correlates with prognosis of colon cancer patients. TIPE1 overexpression significantly inhibits colon cancer cell growth both in vitro and in vivo through impairing stemness, accompanied with downregulation of the stemness-related markers, ALDH, CD133, CD44 and SOX-9. Mechanically, TIPE1 directly targets β-catenin and promotes β-catenin degradation in a protease-dependent manner, and Wnt/β-catenin signaling plays a crucial role during TIPE1-mediated stemness inhibition in colon cancer. These findings reveal that TIPE1 exerts anti-tumor effects in colon cancer and suggest that TIPE1 would be a therapeutic target for cancers.
Identifiants
pubmed: 31111874
pii: 5486062
doi: 10.1093/carcin/bgz079
doi:
Substances chimiques
CTNNB1 protein, human
0
Intracellular Signaling Peptides and Proteins
0
TNFAIP8L1 protein, human
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
25-35Informations de copyright
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.