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Basic Information

Classification Information

Regulatory Mechanism		Biological Function		Clinical Application
TF		Immune		Survival
Enhancer		Apoptosis		Drug
Variant		Cell Growth		Circulating
MiRNA		EMT		Metastasis
Methylation		Coding Ability		Recurrence

Cancer&Entry Information

Cancer Name	breast cancer
ICD-0-3	C50
Methods	qPCR, Western blot
Sample	hTERT-HME1 cells, MDA-MB-231 cells, MCF-7 cells
Expression Pattern	differential expression
Function Description	We define a novel signal- ing loop encompassing canonical and non-canonical actions of EZH2 on the regula- tion of NF-?B/NKILA homeostasis, with relevance to breast cancer treatment. We applied a respective silencing approach in non-transformed breast epithelial cells, triple negative MDA-MB-231 cells and hormone responsive MCF-7 cells, and measured changes in EZH2/NF-?B/NKILA levels to confirm their interdependence. We demonstrate cell line-specific fluctuations in these factors that functionally contribute to epithelial-to-mesenchymal transition (EMT) remodelling and cell fate response. EZH2 inhibition attenuates MDA-MB-231 cell motility and CDK4-medi- ated MCF-7 cell cycle regulation, while inducing global H3K27 methylation and an EMT phenotype in non-transformed cells. Notably, these events are mediated by a cell-context dependent gain or loss of NKILA and NF-?B. Depletion of NF-?B in non- transformed cells enhances their sensitivity to growth factor signaling and suggests a role for the host microenvironment milieu in regulating EZH2/NF-?B/NKILA homeo- stasis.
Pubmed ID	31282094
Year	2019
Title	NF-?B/NKILA signaling modulates the anti-cancerous effects of EZH2 inhibition

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