RBM10 regulates the tumorigenic potential of human cancer cells by modulating PPM1B and YBX1 activities.
Exp Cell Res
; 435(2): 113932, 2024 Feb 15.
Article
de En
| MEDLINE
| ID: mdl-38246397
ABSTRACT
RNA binding protein RBM10 participates in various RNA metabolism, and its decreased expression or loss of function by mutation has been identified in many human cancers. However, how its dysregulation contributes to human cancer pathogenesis remains to be determined. Here, we found that RBM10 expression was decreased in breast tumors, and breast cancer patients with low RBM10 expression presented poorer survival rates. RBM10 depletion in breast cancer cells significantly promotes the cellular proliferation and migration. We further demonstrated that RBM10 forms a triple complex with YBX1 and phosphatase 1B (PPM1B), in which PPM1B serves as the phosphatase of YBX1. RBM10 knock-down markedly attenuated association between YBX1 and PPM1B, leading to elevated levels of YBX1 phosphorylation and its nuclear translocation. Furthermore, cancer cells with RBM10 depletion had a significantly accelerated tumor growth in nude mice. Importantly, these enhanced tumorigenic phenotypes can be reversed by overexpression of PPM1B. Our findings provide the mechanistic bases for functional loss of RBM10 in promoting tumorigenicity, and are potentially useful in the development of combined therapeutic strategies for cancer patients with defective RBM10.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du sein
/
Carcinogenèse
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Female
/
Humans
Langue:
En
Journal:
Exp Cell Res
/
Exp. cell. res
/
Experimental cell research
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
États-Unis d'Amérique