PUBLICATION
Non-POU Domain-Containing Octomer-Binding (NONO) protein expression and stability promotes the tumorigenicity and activation of Akt/MAPK/β-catenin pathways in human breast cancer cells
- Authors
- Lone, B.A., Siraj, F., Sharma, I., Verma, S., Karna, S.K.L., Ahmad, F., Nagar, P., Sachidanandan, C., Pokharel, Y.R.
- ID
- ZDB-PUB-230628-51
- Date
- 2023
- Source
- Cell communication and signaling : CCS 21: 157157 (Journal)
- Registered Authors
- Sachidanandan, Chetana
- Keywords
- Apoptosis, Breast cancer, Cancer stem cells, MAPK/β-catenin, Metastasis, NONO, P53, PIN1
- MeSH Terms
-
- Breast Neoplasms*/pathology
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- DNA-Binding Proteins/metabolism
- Epithelial-Mesenchymal Transition
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- NIMA-Interacting Peptidylprolyl Isomerase/metabolism
- Proto-Oncogene Proteins c-akt/metabolism
- RNA-Binding Proteins/genetics
- Zebrafish/metabolism
- beta Catenin*/metabolism
- PubMed
- 37370134 Full text @ Cell Commun. Signal.
Citation
Lone, B.A., Siraj, F., Sharma, I., Verma, S., Karna, S.K.L., Ahmad, F., Nagar, P., Sachidanandan, C., Pokharel, Y.R. (2023) Non-POU Domain-Containing Octomer-Binding (NONO) protein expression and stability promotes the tumorigenicity and activation of Akt/MAPK/β-catenin pathways in human breast cancer cells. Cell communication and signaling : CCS. 21:157157.
Abstract
Breast cancer is one of the most common cancers with a high mortality rate, underscoring the need to identify new therapeutic targets. Here we report that non-POU domain-containing octamer-binding (NONO) protein is overexpressed in breast cancer and validated the interaction of the WW domain of PIN1 with c-terminal threonine-proline (thr-pro) motifs of NONO. The interaction of NONO with PIN1 increases the stability of NONO by inhibiting its proteasomal degradation, and this identifies PIN1 as a positive regulator of NONO in promoting breast tumor development. Functionally, silencing of NONO inhibits the growth, survival, migration, invasion, epithelial to mesenchymal transition (EMT), and stemness of breast cancer cells in vitro. A human metastatic breast cancer cell xenograft was established in transparent zebrafish (Danio rerio) embryos to study the metastatic inability of NONO-silenced breast cancer cells in vivo. Mechanistically, NONO depletion promotes the expression of the PDL1 cell-surface protein in breast cancer cells. The identification of novel interactions of NONO with c-Jun and β-catenin proteins and activation of the Akt/MAPK/β-catenin signaling suggests that NONO is a novel regulator of Akt/MAPK/β-catenin signaling pathways. Taken together, our results indicated an essential role of NONO in the tumorigenicity of breast cancer and could be a potential target for anti-cancerous drugs. Video Abstract.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping