Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway
| Autor: | Dongdong Cheng, Jing Li, Tao Yu, Hanwei Kong, Fangyu Zhao, Xiao Zhang, Qin Geng, Ming Yao, Miaoxin Zhu, Hechun Lin, Hong Li |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research P65 Immunoprecipitation proliferation Biology NSCLC medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Pharmacology (medical) Nuclear export signal Protein kinase A RC254-282 CSE1L apoptosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens NF-κB MAPK respiratory tract diseases 030104 developmental biology Oncology chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research Molecular Medicine Original Article Signal transduction Carcinogenesis |
| Zdroj: | Molecular Therapy: Oncolytics, Vol 21, Iss, Pp 23-36 (2021) Molecular Therapy Oncolytics |
| 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. Graphical abstract Lin et al. introduce an exportin protein CSE1L that is generally upregulated in NSCLC and is negatively correlated with patients’ prognosis, along with the mechanism of activating the NF-κB/MAPK signaling pathway, which is expected to become a prognostic indicator and effective therapeutic target for NSCLC. |
| Databáze: | OpenAIRE |
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