RIPK1 is a negative mediator in Aquaporin 1-driven triple-negative breast carcinoma progression and metastasis.
Journal
NPJ breast cancer
ISSN: 2374-4677
Titre abrégé: NPJ Breast Cancer
Pays: United States
ID NLM: 101674891
Informations de publication
Date de publication:
12 May 2021
12 May 2021
Historique:
received:
02
07
2020
accepted:
15
04
2021
entrez:
13
5
2021
pubmed:
14
5
2021
medline:
14
5
2021
Statut:
epublish
Résumé
The triple-negative breast carcinoma (TNBC) is the most aggressive subtype of breast cancer. In TNBC, Aquaporin 1 (AQP1), a water-transporting transmembrane protein, is aberrantly enriched in cytoplasm and causes tumor cell death evasion. However, the carcinogenetic bioactivities of cytoplasmic AQP1 cannot be attributed to the canonical "osmotic engine model". In the present study, the receptor-interacting protein kinase 1 (RIPK1), a cell death regulator, was identified to negatively mediate AQP1-driven TNBC progression and metastasis. AQP1 overabundance and RIPK1 depletion occurred in TNBC, which were correlated with aggressive oncological features and poor prognosis. AQP1 bound with RIPK1, resulting in the inhibition of RIPK1/RIPK3/MLKL-mediated necroptosis and RIPK1/caspase-8/caspase-3-mediated apoptosis. Genetic inhibition of RIPK1 significantly exacerbated the pro-tumor effect of AQP1, while ectopic expression of RIPK1 notably blunted AQP1 signaling. Mechanistically, AQP1 binds to the D324 site of RIPK1, and facilitates RIPK1 cleavage and inactivation by excessively activating the caspase-8/RIPK1 negative feedback loop. RIPK1
Identifiants
pubmed: 33980862
doi: 10.1038/s41523-021-00261-5
pii: 10.1038/s41523-021-00261-5
pmc: PMC8115349
doi:
Types de publication
Journal Article
Langues
eng
Pagination
53Subventions
Organisme : National Science Foundation of China | Young Scientists Fund
ID : 81703167
Organisme : National Science Foundation of China | Young Scientists Fund
ID : 81703591
Organisme : National Science Foundation of China | Young Scientists Fund
ID : 81902861
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