MET receptor is a potential therapeutic target in high grade cervical cancer

Miękus, Katarzyna; Pawłowska, Marta; Sekuła, Małgorzata; Drabik, Grażyna; Madeja, Zbigniew; Adamek, Dariusz; Majka, Marcin

doi:10.18632/oncotarget.3161

Cited by 15 publications

(22 citation statements)

References 44 publications

(51 reference statements)

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“…We previously found that E-cadherin expression and the invasive properties of cervical carcinoma depend on the c-Met receptor (46). In this study, we observed an increased level of cMet and strong phosphorylation of the receptor together with the elevated level of kinase Src after MCPIP1 downregulation (Fig.…”

Section: Discussionsupporting

confidence: 65%

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

et al. 2017

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Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL6, IL1, and IL12. MCPIP1 is also a negative regulator of NFkB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patientderived tumors and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth, and vascularity. MCPIP1 activity regulated secretion of VEGF, IL8, and CXCL12 leading to chemotaxis of microvascular endothelial cells, phosphorylation of VEcadherin, and increased vascular permeability. Mechanistic investigations showed that MCPIP1 regulated ccRCC cell motility, lung metastasis, and mesenchymal phenotype by regulating key elements in the EMT signaling axis. Overall, our results illuminate how MCPIP1 serves as a key nodal point in coordinating tumor growth, angiogenesis, and metastatic spread in ccRCC.

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Section: Discussionsupporting

confidence: 65%

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

et al. 2017

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“…Furthermore, MET inhibitor reduced filopodia and lamellipodia formation, thus decreasing migration of these cells . Miekus et al also observed in MET‐deficient cervical carcinoma cells, that F‐actin was located under the cell membrane and did not form regular stress fibres which were present in control cells. Additionally, silencing of MET in cholangiocarcinoma cells led to the disappearance of actin‐rich protrusions induced by HGF .…”

Section: Discussionmentioning

confidence: 93%

“…Furthermore, MET inhibitor reduced filopodia and lamellipodia formation, thus decreasing migration of these cells. 43 Miekus et al 44 and MMP-9-mediated degradation of E-cadherin. 49 Therefore, we also analysed proteolytic activity of generated variants of melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

Pietraszek-Gremplewicz

Simiczyjew

Dratkiewicz

et al. 2019

J Cellular Molecular Medi

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Epidermal and hepatocyte growth factors can stimulate invasive abilities of melanoma cells, while treatment with combination of their receptors' (EGFR and MET, respectively) inhibitors reduces viability of these cells, as we have previously shown. Proposed therapy has potential; however, used drugs block more than one goal effectively, what raises the question about the real target of analysed inhibitors. For this reason, we analysed direct involvement of these receptors in the invasion of melanoma cells inducing EGFR and MET up‐ and down‐regulations in examined cells. Results were acquired with assays evaluating cell migration and invasion (scratch wound assay, Transwell filter‐based method and single‐cell tracking). We revealed that cells' motile abilities are increased after EGFR overexpression and decreased following EGFR and MET silencing. This outcome correlates with elevated (EGFR up‐regulation) or reduced (EGFR/MET down‐regulation) number of formed invadopodia, visualized with immunofluorescence, and their rate of proteolytic abilities, evaluated by fluorescent gelatin degradation assay, and gelatin zymography, compared to control cells. Above‐mentioned data indicate that both—EGFR and MET signalling is directly connected with melanoma cells invasion, what establishes these receptors as promising targets for anti‐cancer treatment.

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“…Our study on rhabdomyosarcoma showed that silencing of the MET receptor stimulates tumor cell differentiation and activation of MET signaling may be the cause of its development and progression (99,100). We have also demonstrated that cervical cancer cells depend on sustained MET activity for their growth and survival and downregulation of MET decreased tumor growth and forced tumor differentiation in vivo (101). Our observation on cervical cancer patient samples revealed that low level of MET accompanied low-grade squamous intraepithelial lesion, whereas increased heavily in high-grade squamous intraepithelial lesion and invasive carcinoma (101) (Fig.…”

Section: Met Receptor and Cancer Stem Cellsmentioning

confidence: 68%

The Met tyrosine kinase receptor as a therapeutic target and a potential cancer stem cell factor responsible for therapy resistance

Miękus

2016

Oncology Reports

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The MET tyrosine kinase receptor plays an important role during tumor development and progression being responsible for proliferation, morphogenetic transformation, cell motility and invasiveness. High expression of the MET receptor has been shown to correlate with increased tumor growth and metastasis, poor prognosis and resistance to radiotherapy. Moreover, MET expression and activation has been shown to be associated with therapy resistance. The occurrence of resistance to targeted therapy might be related to the presence of cancer stem cells (CSCs). CSCs are a subpopulation of cells in the tumor that possess the ability of self-renewal, clonogenicity, radioresistance and self-sustained protection from apoptosis. Recently, MET has been postulated as an essential factor supporting the functional stem cell phenotype in some tumors and as a CSC factor is believed to be responsible for therapy resistance. This review presents the results from recent studies identifying MET as a potential marker of CSCs and tumor initiating cells, demonstrating pivotal role of MET in supporting stem cell phenotype and indicating the role of MET in acquiring resistance to antitumor therapy.

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MET receptor is a potential therapeutic target in high grade cervical cancer

Cited by 15 publications

References 44 publications

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

MCPIP1 Downregulation in Clear Cell Renal Cell Carcinoma Promotes Vascularization and Metastatic Progression

Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

The Met tyrosine kinase receptor as a therapeutic target and a potential cancer stem cell factor responsible for therapy resistance

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