ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer.
Adaptor Proteins, Signal Transducing
/ biosynthesis
Animals
Apoptosis Regulatory Proteins
/ biosynthesis
Cell Line, Tumor
Colorectal Neoplasms
/ genetics
Epithelial-Mesenchymal Transition
Female
HCT116 Cells
Heterografts
Humans
Male
Mice
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Staging
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
received:
14
01
2020
accepted:
18
03
2020
revised:
17
03
2020
entrez:
10
4
2020
pubmed:
10
4
2020
medline:
10
4
2021
Statut:
epublish
Résumé
The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin-dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients.
Identifiants
pubmed: 32269211
doi: 10.1038/s41419-020-2415-2
pii: 10.1038/s41419-020-2415-2
pmc: PMC7142079
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Apoptosis Regulatory Proteins
0
PPP1R13B protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
224Subventions
Organisme : Medical Research Council
ID : MR/S025480/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : SBF002\1038
Pays : United Kingdom
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