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IL-6 promotes metastasis of non-small-cell lung cancer by up-regulating TIM-4 via NF-κB
- Source :
- Cell Proliferation
- Publication Year :
- 2019
-
Abstract
- Objectives Interleukin‐6 (IL‐6) is critical for the development of non‐small‐cell lung cancer (NSCLC). Recently, we identified T‐cell immunoglobulin domain and mucin domain 4 (TIM‐4) as a new pro‐growth player in NSCLC progression. However, the role of TIM‐4 in IL‐6‐promoted NSCLC migration, invasion and epithelial‐to‐mesenchymal transition (EMT) remains unclear. Materials and Methods Expressions of TIM‐4 and IL‐6 were both evaluated by immunohistochemical staining in NSCLC tissues. Real‐time quantitative PCR (qPCR), Western blot, flow cytometry and RT‐PCR were performed to detect TIM‐4 expression in NSCLC cells with IL‐6 stimulation. The roles of TIM‐4 in IL‐6 promoting migration and invasion of NSCLC were detected by transwell assay. EMT‐related markers were analysed by qPCR and Western blot in vitro, and metastasis was evaluated in BALB/c nude mice using lung cancer metastasis mouse model in vivo. Results High IL‐6 expression was identified as an independent predictive factor for TIM‐4 expression in NSCLC tissues. NSCLC patients with TIM‐4 and IL‐6 double high expression showed the worst prognosis. IL‐6 promoted TIM‐4 expression in NSCLC cells depending on NF‐κB signal pathway. Both TIM‐4 and IL‐6 promoted migration, invasion and EMT of NSCLC cells. Interestingly, TIM‐4 knockdown reversed the role of IL‐6 in NSCLC and IL‐6 promoted metastasis of NSCLC by up‐regulating TIM‐4 via NF‐κB. Conclusions TIM‐4 involves in IL‐6 promoted migration, invasion and EMT of NSCLC.
- Subjects :
- 0301 basic medicine
Male
Epithelial-Mesenchymal Transition
Lung Neoplasms
TIM‐4
Mice, Nude
Original Manuscript
Biology
Metastasis
Flow cytometry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Western blot
Carcinoma, Non-Small-Cell Lung
medicine
Animals
Humans
metastasis
Neoplasm Invasiveness
Lung cancer
neoplasms
non‐small‐cell lung cancer
Gene knockdown
Mice, Inbred BALB C
medicine.diagnostic_test
Interleukin-6
NF‐κB
NF-kappa B
Membrane Proteins
NF-κB
Cell Biology
General Medicine
IL‐6
Middle Aged
medicine.disease
respiratory tract diseases
Up-Regulation
Gene Expression Regulation, Neoplastic
030104 developmental biology
Real-time polymerase chain reaction
chemistry
A549 Cells
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Female
Original Manuscripts
Subjects
Details
- ISSN :
- 13652184
- Volume :
- 53
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell proliferation
- Accession number :
- edsair.doi.dedup.....7326b99a593aac2c82ede96955008810