Abstract
BackgroundNon-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most lethal tumour worldwide. Copine 1 (CPNE1) was identified as a novel oncogene in NSCLC in our previous study. However, its specific function and relative mechanisms remain poorly understood.MethodsThe biological role of CPNE1 and RACK1 in NSCLC was investigated using gene expression knockdown and overexpression, cell proliferation assays, clonogenic assays, and Transwell assays. The expression levels of CPNE1, RACK1 and other proteins were determined by western blot analysis. The relationship between CPNE1 and RACK1 was predicted and investigated by mass spectrometry analysis, immunofluorescence staining, and coimmunoprecipitation. NSCLC cells were treated with a combination of a MET inhibitor and gefitinib in vitro and in vivo.ResultsWe found that CPNE1 facilitates tumorigenesis in NSCLC by interacting with RACK1, which further induces activation of MET signaling. CPNE1 overexpression promoted cell proliferation, migration, invasion and MET signaling in NSCLC cells, whereas CPNE1 knockdown produced the opposite effects. In addition, the suppression of the enhancing effect of CPNE1 overexpression on tumorigenesis and MET signaling by knockdown of RACK1 was verified. Moreover, compared to single-agent treatment, dual blockade of MET and EGFR resulted in enhanced reductions in the tumour volume and downstream signaling in vivo.ConclusionsOur findings show that CPNE1 promotes tumorigenesis by interacting with RACK1 and activating MET signaling. The combination of a MET inhibitor with an EGFR-TKI attenuated tumour growth more significantly than either single-drug treatment. These findings may provide new insights into the biological function of CPNE1 and the development of novel therapeutic strategies for NSCLC.3n8P5VYzQLauDz5o6kqwUEVideo
Highlights
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most lethal tumour worldwide
We found that combined targeting of Mesenchymal-epithelial transition tyrosine kinase receptor (MET) and Epidermal growth factor receptor (EGFR) can result in enhanced inhibition of tumorigenesis both in vitro and in vivo, indicating a new therapeutic strategy for treating NSCLC
The role of Copine 1 (CPNE1) in mediating NSCLC cell proliferation, migration and invasion Since our previous study and data from GEPIA database both found that CPNE1 is upregulated in NSCLC and associated with poor prognosis [4, 5] (Additional file 4: Fig S1), we further validated the results of altered expression of CPNE1
Summary
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most lethal tumour worldwide. Copine 1 (CPNE1) was identified as a novel oncogene in NSCLC in our previous study. We found Copine 1 (CPNE1) to be an important oncogene in NSCLC. It is directly targeted by miR-335-5p and promotes cell proliferation and motility in NSCLC [4,5,6]. The A domain has been studied in integrins and several extracellular matrix proteins and appears to function as a protein-binding domain [9]. Though we discovered the expression and function of CPNE1 in NSCLC, few studies have focused on the exact intracellular signaling mechanism. We seek to explore the molecular mechanism by which CPNE1 promotes NSCLC tumorigenesis and executes the CPNE1-centred regulatory network in NSCLC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
