Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells.
Oncogene
; 36(9): 1276-1286, 2017 03 02.
Article
in En
| MEDLINE
| ID: mdl-27546618
ABSTRACT
The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Stem Cells
/
Breast Neoplasms
/
Insulin-Like Growth Factor II
/
Gene Expression Regulation, Neoplastic
/
Inhibitor of Differentiation Protein 1
/
Neoplasm Recurrence, Local
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2017
Document type:
Article
Affiliation country:
Japón