CTHRC1 activates pro-tumorigenic signaling pathways in hepatocellular carcinoma

Wang, Yunpeng; Lee, Mi-Jin; Yu, Goung-Ran; Lee, Hua; Han, Xue-Ji; Kim, Dae‐Ghon

doi:10.18632/oncotarget.22164

Cited by 17 publications

(17 citation statements)

References 34 publications

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“…Typically, it has been reported that the Akt signaling cascade and its up-and downstream molecules including EGFR, ERK1, PI3K, and MMP, etc. can also be modulated by CTHRC1 [24,32]. PI3K/Akt signaling has been shown to have a pivotal role in the proliferation, migration, invasion and EMT in the malignant progression of multiple tumors [33], and the importance of PI3K/Akt signaling in BCa development has been implicated [34].…”

Section: Discussionmentioning

confidence: 99%

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

Cheng

Yan

et al. 2019

Arch Med Sci

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Introduction: Emerging evidence has illustrated that Collagen triple helix repeat containing 1 (CTHRC1) is crucial for tumorigenesis and development. However, the effects of CTHRC1 on bladder cancer progression remain largely unclear. Here, we aim to investigate the function and mechanism of CTHRC1 in behaviors of bladder cancer cells in vitro and in vivo. Material and methods: Interference assays were applied to determine the biological functions of CTHRC1. The expression of CTHRC1 was examined by quantitative real time-PCR (qRT-PCR), Western blot and immunohistochemical (IHC) analysis. Effects of CTHRC1 on proliferation, migration and invasion were evaluated by CCK-8, colony formation, flow cytometry, EdU staining, wound healing, transwell and western blot assays. Bladder cancer cells transfected with sh-CTHRC1 were injected into nude mice to explore the effect of CTHRC1 on tumorigenesis in vivo. Results: CTHRC1 expression was increased in bladder cancer tissues and cell lines compared with normal controls, and associated with advanced clinical stage and lymph node metastasis. Also, patients with high levels of CTHRC1 expression were found to have a poor prognosis. Knockdown of CTHRC1 alleviated bladder cancer cell proliferation, migration and invasion in vitro and impeded tumorigenesis in vivo. Moreover, mechanistic investigation indicated that CTHRC1 could regulate the PI3K/Akt signaling pathway. Conclusions: Our data demonstrated that CTHRC1 played an oncogenic role in bladder cancer by modulating the PI3K/Akt signaling pathway, which sheds novel light on diagnosis and treatment of bladder cancer.

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Section: Discussionmentioning

confidence: 99%

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

Cheng

Yan

et al. 2019

Arch Med Sci

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“…CTHRC1 promotes invasiveness and metastasis of hepatocellular carcinoma through the activation of PI3K/protein kinase B (PKB)/AKT/ERK/cAMP response element-binding protein (CREB) signaling pathway, which induces EMT change and MMP2/MMP9 expression [ 128 ]. CTHRC1 is highly expressed in hepatitis B virus- (HBV-) associated hepatocellular carcinoma.…”

Section: Signaling Pathways Mediated By Cthrc1 Involved In the Promentioning

confidence: 99%

“…As mentioned above, CTHRC1 in hepatocellular carcinoma can induce HIF-1 α to promote tumor angiogenesis and regulate downstream MMPs and tumor suppressor gene p53 by activating the PI3K/AKT signaling pathway [ 128 ]. In human squamous cell carcinoma, HIF-1 α overexpression stimulates VEGF-C upregulation and induces lymphangiogenesis and tumor cell invasion [ 131 ].…”

Section: Signaling Pathways Mediated By Cthrc1 Involved In the Promentioning

confidence: 99%

The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis

Mei

Zhu

Zhang

et al. 2020

Mediators of Inflammation

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Collagen triple helix repeat containing-1 (CTHRC1) has been identified as cancer-related protein. CTHRC1 expresses mainly in adventitial fibroblasts and neointimal smooth muscle cells of balloon-injured vessels and promotes cell migration and tissue repair in response to injury. CTHRC1 plays a pivotal role in some pathophysiological processes, including increasing bone mass, preventing myelination, and reversing collagen synthesis in many tumor cells. The ascended expression of CTHRC1 is related to tumorigenesis, proliferation, invasion, and metastasis in various human malignancies, including gastric cancer, pancreatic cancer, hepatocellular carcinoma, keloid, breast cancer, colorectal cancer, epithelial ovarian cancer, esophageal squamous cell carcinoma, cervical cancer, non-small-cell lung carcinoma, and melanoma. And molecules that regulate the expression of CTHRC1 include miRNAs, lncRNAs, WAIF1, and DPAGT1. Many reports have pointed that CTHRC1 could exert different effects through several signaling pathways such as TGF-β, Wnt, integrin β/FAK, Src/FAK, MEK/ERK, PI3K/AKT/ERK, HIF-1α, and PKC-δ/ERK signaling pathways. As a participant in tissue remodeling or immune response, CTHRC1 may promote early-stage cancer. Several recent studies have identified CTHRC1 as an effectual prognostic biomarker for predicting tumor recurrence or metastasis. It is worth noting that CTHRC1 has different cellular localization and mechanisms of action in different cells and different microenvironments. In this article, we focus on the advances in the signaling pathways mediated by CTHRC1 in tumors.

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“…Our research suggests that PLEK2 and SCN7A may be used as potential biological markers for the early diagnosis of NSCLC. [20,21], MMP12 [22], UBE2T [23], ECT2 [24,25], SULF1 [26], HMGB3 [27], and CTHRC1 [28,29]. Besides, we identified PLEK2 and SCN7A as potential biomarkers of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

PLEK2 and SCN7A: novel biomarkers of non-small cell lung cancer

Liu

Chang

et al. 2020

Preprint

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Background Lung cancer is the leading cause of cancer-related death globally, and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. However, the diagnosis and prognosis of NSCLC remain dim. Our team has focused on identifying differentially expressed genes (DEGs) between NSCLC tissues and adjacent tissues, which may be useful as effective diagnostic markers that can better explain the progression of NSCLC.Methods The Gene Expression Omnibus (GEO) database was used to screen the Gene Expression Omnibus series, which records the information of a large number of patients with primary NSCLC (n > 50). Then, the DEGs were validated using Student’s t -test. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID. The prognosis information was analyzed separately using data obtained from three databases, Human Protein Atlas, Kaplan–Meier Plotter, and SurvExpress.Results A series of 180 DEGs (33 upregulated and 147 downregulated genes), mainly involving genes associated with extracellular exosomes, focal adhesion, and cell adhesion, were identified via GO analysis. Subsequently, KEGG analysis demonstrated that focal adhesion, cell adhesion molecules, and PPAR signaling pathway were the most enriched pathways. Then, we paid particular attention to pleckstrin 2 (PLEK2) and sodium voltage-gated channel alpha subunit 7 (SCN7A), as they have not been investigated as cancer-related genes previously. Kaplan–Meier survival analysis illustrated that PLEK2 and SCN7A levels were significantly correlated with the prognosis of NSCLC.Conclusions Our research found that, as potential biomarkers, both PLEK2 and SCN7A are related to the development and prognosis of NSCLC. They may be used in disease screening and prognosis. The clinical significance of these two genes deserves further investigation.

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CTHRC1 activates pro-tumorigenic signaling pathways in hepatocellular carcinoma

Cited by 17 publications

References 34 publications

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

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

The Role of CTHRC1 in Regulation of Multiple Signaling and Tumor Progression and Metastasis

PLEK2 and SCN7A: novel biomarkers of non-small cell lung cancer

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