CTHRC1 overexpression predicts poor survival and enhances epithelial‐mesenchymal transition in colorectal cancer

Ni, Shujuan; Ren, Fei; Xu, Ming; Tan, Cong; Weng, Wei-Hung; Huang, Zhaohui; Sheng, Weiqi; Huang, Dan

doi:10.1002/cam4.1807

Cited by 48 publications

(42 citation statements)

References 34 publications

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“…CTHRC1 has been reported to be an oncogene in previous studies (21)(22)(23)(24)(25)(26)(27), and it can promote tumorigenesis by multiple mechanisms. It has been confirmed that CTHRC1 can activate the SRC and ERK signal cascades and upregulate the expression of MMP9, thus promoting the invasion of CRC cells (22).…”

Section: Discussionmentioning

confidence: 97%

“…In addition, there is a close relationship between CTHRC1 and EMT. Ni et al (21) demonstrated that CTHRC1 can promote epithelial cell metastasis by inducing the EMT in CRC cells. In a study by Kim et al (22), CTHRC1-knockdown prevented EMT and inhibited the proliferation of renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Kaplan-Meier analysis by Hou et al (61) revealed that patients with epithelial ovarian cancer with high CTHRC1 expression had significantly shorter OS times. Multivariate cox analysis demonstrated that for patients with CRC, CTHRC1 could be used as an independent prognostic factor for OS (21).…”

Section: Discussionmentioning

confidence: 99%

“…One of these proteins, collagen triple helix repeat containing 1 (CTHRC1), was first found to be involved in vascular remodeling and plays a key role in the response of cells to arterial injury (20). CTHRC1 is overexpressed in numerous solid tumors and plays an important role in tumorigenesis and metastasis, particularly in CRC (21,22), gastric cancer, melanoma, oral cancer, pancreatic cancer and hepatocellular cancer (23)(24)(25)(26)(27). CTHRC1 can activate multiple signaling pathways and promote epithelial cell metastasis by inducing the EMT in CRC (21).…”

Section: Cyclovirobuxine D Inhibits Colorectal Cancer Tumorigenesis Vmentioning

confidence: 99%

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Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

et al. 2020

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Cyclovirobuxine D (CVB-D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB-D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB-D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB-D and further elucidate its molecular mechanism(s). DLD-1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB-D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB-D-treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB-D in vivo. It was identified that CVB-D inhibited the proliferation, migration, stemness, angiogenesis and epithelial-mesenchymal transition of CRC cells, and induced apoptosis and S-phase arrest. In addition, CVB-D significantly inhibited the growth of xenografts. It is notable that CVB-D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB-D exerted anticancer effects through the CTHRC1-AKT/ERK-Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB-D may offer a promising novel therapeutic approach for CRC treatment.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cyclovirobuxine D Inhibits Colorectal Cancer Tumorigenesis Vmentioning

confidence: 99%

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Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

et al. 2020

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“…CTHRC1 encodes a protein that may play a role in the cellular response to arterial injury through involvement in vascular remodeling [19]. Previous studies had shown that CTHRC1 promoted tumor cell progression and might play a key role in the invasion and metastasis of cervical carcinoma, cervical squamous cell carcinoma and colorectal cancer [20][21][22]. In addition, CTHRC1 promotes M2-like macrophage recruitment and myometrial invasion in endometrial carcinoma by integrin-Akt signaling pathway [23], which indicated that CTHRC1 might be a biomarker for tumor immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

A prognostic model constructed by CTHRC1 and LRFN4 in Stomach adenocarcinoma by Bioinformatics Analysis

Han

Zhu

Guan

et al. 2020

Preprint

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Background Stomach adenocarcinoma (STAD) is the most common histological type of stomach cancer, which causes a considerable number of deaths worldwide. This study specifically aimed to identify potential biomarkers and reveal the underlying molecular mechanisms. Methods Gene expression profiles microarray data were downloaded from the Gene Expression Omnibus (GEO) database. The ‘limma’ R package was used to screen the differentially expressed genes (DEGs) between STAD and matched normal tissues. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for function enrichment analyses of DEGs. The data of STAD cases with both RNA sequencing and clinical information of The Cancer Genome Atlas (TCGA) were obtained from Genomic Data Commons (GDC) data portal. Survival curves were analyzed by the Kaplan-Meier method, univariate Cox regression analysis and multivariate Cox regression were performed using ‘survival’ package. CIBERSORT algorithm used approach to characterize the 22 human immune cell composition. Gene expression profiles microarray data and clinical information were downloaded from GEO database to validate prognostic model. Results Three public datasets including 90 STAD patients and 43 healthy controls were used and 44 genes were differentially expressed in all three datasets. These genes were primarily implicated in biological processes including cell adhesion, wound healing and extracellular matrix organization. Seven out of 44 genes showed significant survival differences based on their expression differences. CTHRC1 and LRFN4 were eventually used to constructed risk score and prognostic model by univariate Cox regression and stepwise multivariate Cox regression in The Cancer Genome Atlas (TCGA)-STAD dataset. The group having high risk scores and the group having low risk scores had significant differences in the infiltration level of multiple immune cells including CD4 memory resting T cells, M2 macrophages, memory B cells, resting dendritic cells, eosinophils, and gamma delta T cells. Multivariate Cox regression analyses indicated that the risk score was an independent predictor after adjusting for age, sex, and tumor stage. At last, the model was verified and evaluated by another independent dataset and showed a good classification effect. Conclusions The present study constructed the prognostic model by expression of CTHRC1 and LRFN4 for the first time via comprehensive bioinformatics analysis, which may provide clinical guidance and potential therapeutic targets for STAD.

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The impact of SOX4‐activated CTHRC1 transcriptional activity regulating DNA damage repair on cisplatin resistance in lung adenocarcinoma

Ai,

Huang,

Rong

et al. 2024

Electrophoresis

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Lung adenocarcinoma (LUAD) is the predominant subtype within the spectrum of lung malignancies. CTHRC1 has a pro‐oncogenic role in various cancers. Here, we observed the upregulation of CTHRC1 in LUAD, but its role in cisplatin resistance in LUAD remains unclear. Bioinformatics analysis was employed to detect CTHRC1 and SRY‐related HMG‐box 4 (SOX4) expression in LUAD. Gene Set Enrichment Analysis predicted the enriched pathways related to CTHRC1. JASPAR and MotifMap databases predicted upstream transcription factors of CTHRC1. Pearson analysis was conducted to analyze the correlation between genes of interest. The interaction and binding relationship between CTHRC1 and SOX4 were validated through dual‐luciferase and chromatin immunoprecipitation assays. Quantitative real‐time polymerase chain reaction determined the expression of CTHRC1 and SOX4 genes. CCK‐8 was performed to assess cell viability and calculate IC50 value. Flow cytometry examined the cell cycle. Comet assay and western blot assessed DNA damage. CTHRC1 and SOX4 were upregulated in LUAD. CTHRC1 exhibited higher expression in cisplatin‐resistant A549 cells compared to cisplatin‐sensitive A549 cells. Knockdown of CTHRC1 enhanced DNA damage during cisplatin treatment and increased the sensitivity of LUAD cells to cisplatin. Additionally, SOX4 modulated DNA damage repair (DDR) by activating CTHRC1 transcriptional activity, promoting cisplatin resistance in LUAD cells. SOX4 regulated DDR by activating CTHRC1, thereby enhancing cisplatin resistance in LUAD cells. The finding provides a novel approach to address clinical cisplatin resistance in LUAD, with CTHRC1 possibly serving as a candidate for targeted therapies in addressing cisplatin resistance within LUAD.

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CTHRC1 overexpression predicts poor survival and enhances epithelial‐mesenchymal transition in colorectal cancer

Cited by 48 publications

References 34 publications

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

A prognostic model constructed by CTHRC1 and LRFN4 in Stomach adenocarcinoma by Bioinformatics Analysis

The impact of SOX4‐activated CTHRC1 transcriptional activity regulating DNA damage repair on cisplatin resistance in lung adenocarcinoma

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