The Involvement of Hepatocyte Growth Factor-MET-Matrix Metalloproteinase 1 Signaling in Bladder Cancer Invasiveness and Proliferation. Effect of the MET Inhibitor, Cabozantinib (XL184), on Bladder Cancer Cells

Shintani, Terumichi; Kusuhara, Yoshito; Daizumoto, Kei; Dondoo, Tsogt-Ochir; Yamamoto, Hiroki; Mori, Hideki; Fukawa, Tomoya; Nakatsuji, Hiroyoshi; Fukumori, Tomoharu; Takahashi, Masayuki; Kanayama, Hiro‐omi

doi:10.1016/j.urology.2016.12.006

Cited by 16 publications

(16 citation statements)

References 20 publications

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“…As a heterodimeric transmembrane receptor tyrosine kinase, MET mediates the activation of multiple signaling pathways, including PI3K/AKT, Ras-Rac/Rho and phospholipase C-γ pathways [31]. Signi cantly higher level of MET was detected in PTC [32,33], non-small cell lung cancer [34], bladder cancer [35] and oral cancer [36]. Those results all add up to a better proof of MET as a cancerpromoting factor and can be corroborated with our ndings.…”

Section: Discussionsupporting

confidence: 88%

Development of A Three-Gene Signature Prediction Model for Lymph Node Metastasis in Papillary Thyroid Cancer

Huang

Liu

et al. 2020

Preprint

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Background: Thyroid cancer is one of the most prevalent endocrine cancers with a rising incidence rate over the past years. Papillary thyroid cancer (PTC) is the dominant historical type of thyroid cancer. Early lymph node metastasis happens frequently in PTC. However, some of the lymph node metastasis may be troublesome for detecting because of limited methods.Methods: Robust rank aggregation afforded us the shared differential expression genes among multiple datasets. Gene ontology analysis was performed to identify potential functions. Weighted gene co-expression network analysis was used to research the correlations between gene expression patterns with clinical characteristic. Protein-protein interaction network was performed to identify the hub genes. The least absolute shrinkage and selection operator and Logistic regression were performed to construct a prediction model.Results: We developed a three-gene signature prediction model for lymph node metastasis in PTC through transcriptomic analysis. After quality control, we collected 8 microarray datasets from GEO database and an RNA sequencing dataset from TCGA database. We found the transcriptome profiles were correlated with lymph node metastasis and 3 genes were verified to be independent prediction factors towards those statistic approach. Afterwards, we designed a predicable risk score system and effectively confirmed the model in two independent papillary thyroid cancer cohorts.Conclusions: We recommended a successful predicable model of lymph node metastasis in papillary thyroid cancer patients with moderate accuracy.

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Section: Discussionsupporting

confidence: 88%

Development of A Three-Gene Signature Prediction Model for Lymph Node Metastasis in Papillary Thyroid Cancer

Huang

Liu

et al. 2020

Preprint

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“…This implies that far from acting alone, these proteases assemble in cascades of zymogens, activators, inhibitors, and other bioactive substrates; in which proteolytic cleavage modulates the potential of the entire system with far-reaching effects, affecting other MMPs, as well as their substrates and functions. Given their multifaceted properties, MMPs regulate cell proliferation, adhesion, migration [15], growth factor bioavailability, chemotaxis, and signaling; and they are crucial for angiogenesis, vasodilation, tumorigenesis [16], metastasis [17], immunity, inflammation, and wound healing [13]. …”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinases as Regulators of Periodontal Inflammation

Cavalla

Patricia

Sorsa

et al. 2017

IJMS

239

196

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Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation.

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“…As a biomarker, the utility of urinary soluble MET concentration to detect bladder cancer and MIBC was reported [101,102]. In vitro analysis, efficient suppression of invasion and proliferation by cabozantinib (dual inhibitor of MET and VEGFR) was observed in invasive UC cell lines (5637, T24) [103]. HGF/MET signaling-induced expression of MMP-1 was also suppressed by cabozantinib in the same cell lines.…”

Section: Significance Of Hgf-dependent Met Activation In Muscle Invasmentioning

confidence: 99%

“…HGF/MET signaling-induced expression of MMP-1 was also suppressed by cabozantinib in the same cell lines. HGF/MET signaling-induced EMT is a major phenomenon in various cancer cells [103]. Recently, it has been reported that HGF/MET signaling-induced inhibition of SMURF2 yielded stabilization of TGF-β receptor, and that upregulation of TGF-β signaling axis leads to EMT of UC cell line [104].…”

Section: Significance Of Hgf-dependent Met Activation In Muscle Invasmentioning

confidence: 99%

“…These findings suggested that HAI-1 may regulate the ligand-dependent activation of MET in patients with MIBC. As a biomarker, the utility of urinary soluble MET concentration to detect bladder cancer and MIBC was reported [102,103]. In vitro analysis, efficient suppression of invasion and proliferation by cabozantinib (dual inhibitor of MET and VEGFR) was observed in invasive UC cell lines (5637, T24) [104].…”

Section: Significance Of Hgf-dependent Met Activation In Muscle Invasmentioning

confidence: 99%

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Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers

Mukai

Yamasaki

Fujisawa

et al. 2020

IJMS

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Unlike in normal epithelium, dysregulated overactivation of various proteases have been reported in cancers. Degradation of pericancerous extracellular matrix leading to cancer cell invasion by matrix metalloproteases is well known evidence. On the other hand, several cell-surface proteases, including type II transmembrane serine proteases (TTSPs), also induce progression through activation of growth factors, protease activating receptors and other proteases. Hepatocyte growth factor (HGF) known as a multifunctional growth factor that upregulates cancer cell motility, invasiveness, proliferative, and anti-apoptotic activities through phosphorylation of MET (a specific receptor of HGF). HGF secreted as inactive zymogen (pro-HGF) from cancer associated stromal fibroblasts, and the proteolytic activation by several TTSPs including matriptase and hepsin is required. The activation is strictly regulated by HGF activator inhibitors (HAIs) in physiological condition. However, downregulation is frequently observed in cancers. Indeed, overactivation of MET by upregulation of matriptase and hepsin accompanied by the downregulation of HAIs in urological cancers (prostate cancer, renal cell carcinoma, and bladder cancer) are also reported, a phenomenon observed in cancer cells with malignant phenotype, and correlated with poor prognosis. In this review, we summarized current reports focusing on TTSPs, HAIs, and MET signaling axis in urological cancers.

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The Involvement of Hepatocyte Growth Factor-MET-Matrix Metalloproteinase 1 Signaling in Bladder Cancer Invasiveness and Proliferation. Effect of the MET Inhibitor, Cabozantinib (XL184), on Bladder Cancer Cells

Cited by 16 publications

References 20 publications

Development of A Three-Gene Signature Prediction Model for Lymph Node Metastasis in Papillary Thyroid Cancer

Development of A Three-Gene Signature Prediction Model for Lymph Node Metastasis in Papillary Thyroid Cancer

Matrix Metalloproteinases as Regulators of Periodontal Inflammation

Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers

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