Nature communications, 2019-12, Vol.10 (1), p.5720-16, Article 5720
2019
Details
- Autor(en) / Beteiligte
- Titel
- TRIB3 supports breast cancer stemness by suppressing FOXO1 degradation and enhancing SOX2 transcription
- Ist Teil von
- Nature communications, 2019-12, Vol.10 (1), p.5720-16, Article 5720
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence after chemotherapy and radiotherapy. Targeting BCSCs may ameliorate breast cancer relapse and therapy resistance. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) positively associates with breast cancer stemness and progression. Elevated TRIB3 expression supports BCSCs by interacting with AKT to interfere with the FOXO1-AKT interaction and suppress FOXO1 phosphorylation, ubiquitination, and degradation by E3 ligases SKP2 and NEDD4L. The accumulated FOXO1 promotes transcriptional expression of SOX2, a transcriptional factor for cancer stemness, which in turn, activates FOXO1 transcription and forms a positive regulatory loop. Disturbing the TRIB3-AKT interaction suppresses BCSCs by accelerating FOXO1 degradation and reducing SOX2 expression in mouse models of breast cancer. Our study provides insights into breast cancer development and confers a potential therapeutic strategy against TRIB3-overexpressed breast cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-13700-6Titel-ID: cdi_doaj_primary_oai_doaj_org_article_b1e7a79e5d3d4b7f8ef165185b467013
- Format
- –
- Schlagworte
- AKT protein, Animals, Breast - pathology, Breast cancer, Breast Neoplasms - genetics, Breast Neoplasms - pathology, Cell Cycle Proteins - metabolism, Cell Line, Tumor, Disease Progression, Female, Forkhead Box Protein O1 - metabolism, FOXO1 protein, Gene Expression Regulation, Neoplastic, Humans, Metastases, Mice, Middle Aged, Neoplastic Stem Cells - pathology, Protein Binding, Protein-Serine-Threonine Kinases - antagonists & inhibitors, Protein-Serine-Threonine Kinases - metabolism, Proteolysis, Proto-Oncogene Proteins c-akt - metabolism, Repressor Proteins - metabolism, SOXB1 Transcription Factors - genetics, Stem cells, Tissue Array Analysis, Transcription, Transcription, Genetic, Xenograft Model Antitumor Assays