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CBX7 binds the E-box to inhibit TWIST-1 function and inhibit tumorigenicity and metastatic potential
- Source :
- Oncogene
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Deaths from ovarian cancer usually occur when patients succumb to overwhelmingly numerous and widespread micrometastasis. Whereas epithelial-mesenchymal transition is required for epithelial ovarian cancer cells to acquire metastatic potential, the cellular phenotype at secondary sites and the mechanisms required for the establishment of metastatic tumors are not fully determined. Using in vitro and in vivo models we show that secondary epithelial ovarian cancer cells (sEOC) do not fully re-acquire the molecular signature of the primary epithelial ovarian cancer cells from which they are derived. Despite displaying an epithelial morphology, sEOC maintains a high expression of the mesenchymal effector, TWIST-1. TWIST-1 is however transcriptionally non-functional in these cells as it is precluded from binding its E-box by the PcG protein, CBX7. Deletion of CBX7 in sEOC was sufficient to reactivate TWIST-1-induced transcription, prompt mesenchymal transformation, and enhanced tumorigenicity in vivo. This regulation allows secondary tumors to achieve an epithelial morphology while conferring the advantage of prompt reversal to a mesenchymal phenotype upon perturbation of CBX7. We also describe a sub-classification of ovarian tumors based on CBX7 and TWIST-1 expression, which predicts clinical outcomes and patient prognosis.
- Subjects :
- mesenchymal-epithelial transition
0301 basic medicine
Cancer Research
Epithelial-Mesenchymal Transition
Transcription, Genetic
Carcinogenesis
E-box
Biology
Response Elements
Article
03 medical and health sciences
0302 clinical medicine
In vivo
Transcription (biology)
Cell Line, Tumor
Genetics
medicine
Humans
metastasis
Neoplasm Metastasis
Molecular Biology
Ovarian Neoplasms
Polycomb Repressive Complex 1
Effector
Twist-Related Protein 1
Micrometastasis
Mesenchymal stem cell
Nuclear Proteins
medicine.disease
In vitro
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
ovarian cancer
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
Female
Ovarian cancer
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....d08459b520d999047c7fdb118382254a