Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway

Autor: H.C. Lin, J. Li, D.D. Cheng, X. Zhang, T. Yu, F.Y. Zhao, Q. Geng, M.X. Zhu, H.W. Kong, H. Li, M. Yao
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Molecular Therapy: Oncolytics, Vol 21, Iss , Pp 23-36 (2021)
Druh dokumentu: article
ISSN: 2372-7705
DOI: 10.1016/j.omto.2021.02.015
Popis: Non-small cell lung cancer (NSCLC) is characterized with high morbidity and mortality, mainly due to frequent recurrence and metastasis. However, the underlying molecular mechanisms of NSCLC tumorigenesis are largely unclear. Through data mining in the ONCOMINE and Gene Expression Omnibus (GEO) databases, the expression of CSE1L (chromosome segregation like 1 protein/CAS), an exportin, was identified to be significantly upregulated in NSCLC and positively associated with poor prognosis of patients. By use of in vitro and in vivo gain- and loss-of-function experiments, we found that CSE1L can promote NSCLC cell proliferation while inhibiting cell apoptosis. Through immunoprecipitation and mass spectrometry experiments, we demonstrated that CSE1L interacted with RELA (named as P65) and affected its location in the nucleus. Moreover, we found that one of the mechanisms by which CSE1L promotes proliferation and inhibits apoptosis is through activating the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. In summary, our findings indicated an oncogenic role of CSE1L in NSCLC tumorigenesis.
Databáze: Directory of Open Access Journals