HGF-activated colonic fibroblasts mediates carcinogenesis of colonic epithelial cancer cells via PKC-cMET-ERK1/2-COX-2 signaling

Li, F.; Zhu, Yingting

doi:10.1016/j.cellsig.2015.01.014

Cited by 24 publications

(12 citation statements)

References 29 publications

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“…These differential effects of NMII activity on endothelial cell–cell junctions are also observed in cancer metastasis, where tumor cells increase endothelial NMII activity, disrupting adhesions and allowing for transcellular migration and tissue invasion ( Khuon et al, 2010 ; Li and Zhu, 2015 ; Li et al, 2015a ). For example, melanoma cells increase endothelial cell contractility in vitro , leading to the rupture of cell–cell adhesion by the simultaneous activation of VCAM and IL1β- and IL8-mediated signaling pathways ( Weidert et al, 2014 ).…”

Section: Myosin and Vascular Diseasesmentioning

confidence: 80%

Non-muscle myosin II in disease: mechanisms and therapeutic opportunities

Litwa

Horwitz

Lamers

2015

Disease Models &Amp; Mechanisms

126

115

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The actin motor protein non-muscle myosin II (NMII) acts as a master regulator of cell morphology, with a role in several essential cellular processes, including cell migration and post-synaptic dendritic spine plasticity in neurons. NMII also generates forces that alter biochemical signaling, by driving changes in interactions between actin-associated proteins that can ultimately regulate gene transcription. In addition to its roles in normal cellular physiology, NMII has recently emerged as a critical regulator of diverse, genetically complex diseases, including neuronal disorders, cancers and vascular disease. In the context of these disorders, NMII regulatory pathways can be directly mutated or indirectly altered by disease-causing mutations. NMII regulatory pathway genes are also increasingly found in disease-associated copy-number variants, particularly in neuronal disorders such as autism and schizophrenia. Furthermore, manipulation of NMII-mediated contractility regulates stem cell pluripotency and differentiation, thus highlighting the key role of NMII-based pharmaceuticals in the clinical success of stem cell therapies. In this Review, we discuss the emerging role of NMII activity and its regulation by kinases and microRNAs in the pathogenesis and prognosis of a diverse range of diseases, including neuronal disorders, cancer and vascular disease. We also address promising clinical applications and limitations of NMII-based inhibitors in the treatment of these diseases and the development of stem-cell-based therapies.

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Section: Myosin and Vascular Diseasesmentioning

confidence: 80%

Non-muscle myosin II in disease: mechanisms and therapeutic opportunities

Litwa

Horwitz

Lamers

2015

Disease Models &Amp; Mechanisms

126

115

View full text Add to dashboard Cite

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“…HGF and its receptor, c-Met (tyrosine-protein kinase Met or hepatocyte growth factor receptor), are involved in a number of important biological processes (43). HGF/c-Met interaction has been implicated in HGF-activated colonic fibroblast-mediated carcinogenesis of colonic epithelial cancer cells (44,45). The higher levels of c-Met mRNA and protein in CRC liver metastasis, the positive correlation between c-Met expression and liver metastasis, and the association of the downregulation of HGF/c-Met signalling with the reduction in cell proliferation, invasion and metastasis of liver cancer, indicate a potentially crucial role of HGF in CRC (46).…”

Section: Discussionmentioning

confidence: 99%

Expression of VEGF, EGF and HGF in early‑ and late‑stage colorectal cancer

et al. 2021

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The heterogenous nature of colorectal cancer (CRC) highlights the need for a better understanding of the growth factors that affect tumour growth and cancer progression. The aim of the present study was to evaluate the role of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in the early (I and II) and late (III and IV) stages of CRC. The serum levels and mRNA expression (n=30) of the aforementioned growth factors were measured and immunohistochemistry (n=20) was performed in patients with CRC. Histological examination revealed comparable distribution of early-stage [I: 8 (26.7%) and II: 7 (23.3%)] and late-stage [III: 8 (26.7%) and IV: 7 (23.3%)] CRC. The mean serum concentrations of VEGF during the early (152.9±14.5 vs. 88.39±3.99 pg/ml; P=0.001) and late (182.7±25.8 vs. 88.39±3.99 pg/ml; P=0.002) stages were significantly higher compared with those in controls. Similarly, the mean serum concentrations of EGF in the early (409.4±7.96 vs. 153.7±13.8 pg/ml; P=0.05) and HGF in the late (90.4±17.4 vs. 56.9±4.97 pg/ml; P=0.05) stages were significantly higher compared with those in controls. The serum concentrations of VEGF, EGF and HGF were comparable between the early and late stages of CRC. Compared to normal tissues, the mRNA expression of both VEGF (P<0.001) and HGF (P<0.01) was upregulated in early-stage and downregulated in late-stage CRC. The expression of EGF remained significantly elevated during both the early and late stages of CRC (P<0.01). Histopathological analyses confirmed increased expression of VEGF in cancerous tissues compared with that in normal tissues. The present study emphasized the need for monitoring the serum levels and tissue expression of growth factors to fully elucidate their role in patients with CRC.

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“…[29] Third, a high expression of both COX-2 and C-MET had synergistic effects in regulating the malignant behavior of CRC, and these proteins are important markers for invasion and metastasis as well as potential molecular targets for specific treatments. [3031] In addition, OS is the consequence of multiple effects, not only including therapeutic options but also the natural behaviors of the tumor. Thus, KRAS status was informative for both PFS and OS.…”

Section: Discussionmentioning

confidence: 99%

COX-2/C-MET/KRAS status-based prognostic nomogram for colorectal cancer: A multicenter cohort study

Liu

Huang

Wang

et al. 2019

Saudi J Gastroenterol

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Background/Aim:To construct quantitative prognostic models for colorectal cancer (CRC) based on COX-2/C-MET/KRAS expression status in clinical practice.Patients and Methods:Clinical factors and COX-2/C-MET/KRAS expression status of 578 eligible patients from two Chinese hospitals were included. The patients were randomly allocated into training and validation datasets. We created several models using Cox proportional hazard models: SignatureC contained clinical factors, SignatureG contained COX-2/C-MET/KRAS expression status, and SignatureCG contained both. After comparing their accuracy, nomograms for progression-free survival (PFS) and overall survival (OS) were built for the best signatures, with their concordance index and calibration tested. Further, patients were subgrouped by the median of the best signatures, and survival differences between the subgroups were compared.Results:For PFS, among the three signatures, SignaturePFS-CG had the best area under the curve (AUC), with the 1-, 2- and 3-year AUCs being 0.70, 0.73 and 0.89 in the training dataset, respectively and 0.67, 0.73 and 0.87 in the validation dataset, respectively. For OS, the AUCs of SignatureOS-CG for 1-, 2- and 3-years were 0.63, 0.71 and 0.81 in the training dataset, respectively and 0.68, 0.71 and 0.76 in validation dataset, respectively. The nomograms based on SignaturePFS-CG and SignatureOS-CG had good calibrations. Subsequent stratification analysis demonstrated that the subgroups were significantly different for both PFS (training: P < 0.001; validation: P < 0.001) and OS (training: P < 0.001; validation: P < 0.001).Conclusions:Combining clinical factors and COX-2/C-MET/KRAS expression status, our models provided accurate prognostic information in CRC. They can be used to aid treatment decisions in clinical practice.

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HGF-activated colonic fibroblasts mediates carcinogenesis of colonic epithelial cancer cells via PKC-cMET-ERK1/2-COX-2 signaling

Cited by 24 publications

References 29 publications

Non-muscle myosin II in disease: mechanisms and therapeutic opportunities

Non-muscle myosin II in disease: mechanisms and therapeutic opportunities

Expression of VEGF, EGF and HGF in early‑ and late‑stage colorectal cancer

COX-2/C-MET/KRAS status-based prognostic nomogram for colorectal cancer: A multicenter cohort study

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