CPNE1 promotes non-small cell lung cancer progression by interacting with RACK1 via the MET signaling pathway

Abstract

Background 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. However, its specific function and relative mechanisms remain poorly understood. Methods The 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. Results We 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. Conclusions Our 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.

Comprehensive analysis of prognostic value, immune implication and biological function of CPNE1 in clear cell renal cell carcinoma

“…EGFR signaling play an important role in tumorigenesis and progression ( Tomas et al, 2014 ). Previous studies showed that CPNE1 is a critical factor in the tumorigenesis of lung cancer and that its mechanism involves the EGFR signaling pathway ( Tang et al, 2018a ; Wang et al, 2022 ). Therefore, we detected the effect of CPNE1 on the regulation of EGFR signaling pathway in ccRCC.…”

RACK1 may participate in placental development via regulating proliferation and migration of trophoblast cell in pigs following intrauterine growth restriction

“…This finding is consistent with the results of enrichment analysis of DEGs between the MW and LW placentas in the present study. Furthermore, studies on model animals have confirmed that knockdown of RACK1 suppresses cell growth in cultured cells and homozygous knockout of RACK1 is lethal for the embryo [45][46][47]. A recent study on pigs has shown that the proliferation and invasion of trophoblast cells affect the formation and development of PFs [27].…”

Exploration of Ginkgo biloba leaves on non-small cell lung cancer based on network pharmacology and molecular docking

“…[41] Luteolin is a flavonoid abundant in fruits and vegetables, study has proved that it can improve anti-tumor immunity in KRAS-mutant lung cancer, [42] and inhibit the migration and invasion of NSCLC through MAPK and PI3K/Akt pathways. [43] Kaempferol, a flavonoid from natural plant sources, has proved to be effective in anti-NSCLC, specifically in inducing apoptosis in NSCLC cells, [44] promoting autophagy in NSCLC cells, [45] increasing the sensitivity to radiotherapy, [46] and inhibiting migration of A549 cells. [47] The PI3K-AKT signaling pathway is a key signaling pathway that regulates the progression of metastasis, [48] cell proliferation, differentiation, and metabolism.…”