Abstract
BackgroundThe strong invasive and metastatic nature of non-small cell lung cancer (NSCLC) leads to poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) is involved in cell migration, motility and invasion. The object of this study is to investigate the involvement of CTHRC1 in NSCLC invasion and metastasis.MethodsA proteomic analysis was performed to identify the different expression proteins between NSCLC and normal tissues. Cell lines stably express CTHRC1, MMP7, MMP9 were established. Invasion and migration were determined by scratch and transwell assays respectively. Clinical correlations of CTHRC1 in a cohort of 230 NSCLC patients were analysed.ResultsCTHRC1 is overexpressed in NSCLC as measured by proteomic analysis. Additionally, CTHRC1 increases tumour cell migration and invasion in vitro. Furthermore, CTHRC1 expression is significantly correlated with matrix metalloproteinase (MMP)7 and MMP9 expression in sera and tumour tissues from NSCLC. The invasion ability mediated by CTHRC1 were mainly MMP7- and MMP9-dependent. MMP7 or MMP9 depletion significantly eradicated the pro-invasive effects mediated by CTHRC1 on NSCLC cells. Clinically, patients with high CTHRC1 expression had poor survival.ConclusionsCTHRC1 serves as a pro-metastatic gene that contributes to NSCLC invasion and metastasis, which are mediated by upregulated MMP7 and MMP9 expression. Targeting CTHRC1 may be beneficial for inhibiting NSCLC metastasis.
Highlights
The strong invasive and metastatic nature of non-small cell lung cancer (NSCLC) leads to poor prognosis
Collagen triple helix repeat containing 1 (CTHRC1) overexpression in NSCLC tissues correlates with clinical metastasis status in NSCLC Comparative proteomic analysis simultaneously revealed 34 differential spots in NSCLC tissues compared with corresponding adjacent non-tumour tissues (ANTs)
We confirmed that CTHRC1 is overexpressed in all the NSCLC cell lines (Additional file 1: Figure S1B)
Summary
The strong invasive and metastatic nature of non-small cell lung cancer (NSCLC) leads to poor prognosis. The object of this study is to investigate the involvement of CTHRC1 in NSCLC invasion and metastasis. Tumor metastasis is a complex process involving cell adhesion and proteolytic degradation of the extracellular matrix (ECM) [7, 8]. Matrix metalloproteinases (MMPs) are characterized by their ability to degrade extracellular matrix (ECM) proteins and expose cryptic sites within. He et al BMC Cancer (2018) 18:400 the matrix molecules to facilitate tumour invasion and metastasis [9,10,11,12]. To further understand MMP modulation mechanisms in NSCLC to search for new therapeutic targets is imperative
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