CTHRC1 induces non-small cell lung cancer (NSCLC) invasion through upregulating MMP-7/MMP-9

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.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4317-6) contains supplementary material, which is available to authorized users.

CTHRC1 facilitates bladder cancer cell proliferation and invasion through regulating the PI3K/Akt signaling pathway

“…CTHRC1 was as originally found as an extracellular matrix glycoprotein during the arterial injury-repair process [5], which has been shown to modulate vascular remodeling, osteoblastic bone formation and cell migration [6,20]. In addition, CTHRC1 serves as a prognostic factor involved in driving human tumor progression [21][22][23][24][25]. In accordance with this evidence, we observed that CTHRC1 mRNA and protein were dramatically upregulated in both clinical samples and BCa Arch Med Sci cells.…”

Transcriptomic profiling of fibropapillomatosis in green sea turtles (Chelonia mydas) from South Texas

“…50 Increased expression of MMP9 was associated with poorer outcomes in nasopharyngeal carcinoma patients 52 and together with increased expression of CTHCR1 and MMP7 , higher expression of MMP9 was associated with a lower survival rate after surgery in non-small cell lung cancer patients. 53 This known connection between CTHCR1 and MMP7/MMP9 is reflected in the current study, with significant upregulation of CTHRC1 in FP tumors accompanied by increased expression of MMP7 (log2FoldChange = 4.26, padj = 8.87×10 −9 ) and MMP9 (log2FoldChange = 4.24, padj = 4.05×10 −8 ) (supplementary table 1). Together this suggests that CTHRC1 may be a key oncogenic driver in FP.…”

A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors

“…The Kaplan-Meier analysis results showed that higher levels of MMP9, CSF1R, and PTPRC were related to shorter survival time of TGCT patients. MMP9 is a class of enzymes involved in the degradation of the extracellular matrix, which was up-regulated in tumor tissue samples of multi cancer [59][60][61], such as TGCT [62], breast cancer [63], lung cancer [64]. Moreover, MMP9 overexpression was significantly associated with poor survival of nasopharyngeal carcinoma [65] and glioblastoma [66].…”