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.

Autor: Lone BA; Cancer Biology Laboratory, Faculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidangarhi, New Delhi, 110068, India., Siraj F; National Institute of Pathology, Safdarjung Hospital Campus, Room No.610, 6th Floor, Ansari Nagar, New Delhi, 110029, India., Sharma I; National Institute of Pathology, Safdarjung Hospital Campus, Room No.610, 6th Floor, Ansari Nagar, New Delhi, 110029, India., Verma S; CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi, 110025, India.; Academy of Scientific and Innovative Research (AcSIR), Gaziabad, 201002, India., Karna SKL; Cancer Biology Laboratory, Faculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidangarhi, New Delhi, 110068, India., Ahmad F; Cancer Biology Laboratory, Faculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidangarhi, New Delhi, 110068, India., Nagar P; Cancer Biology Laboratory, Faculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidangarhi, New Delhi, 110068, India., Sachidanandan C; CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi, 110025, India.; Academy of Scientific and Innovative Research (AcSIR), Gaziabad, 201002, India., Pokharel YR; Cancer Biology Laboratory, Faculty of Life Science and Biotechnology, South Asian University, Rajpur Road, Maidangarhi, New Delhi, 110068, India. yrp@sau.ac.in.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2023 Jun 27; Vol. 21 (1), pp. 157. Date of Electronic Publication: 2023 Jun 27.
DOI: 10.1186/s12964-023-01179-0
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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