Paradoxical action of growth factors: antiproliferative and proapoptotic signaling by HGF/c-MET

Grzelakowska-Sztabert, Barbara; Dudkowska, Magdalena

doi:10.3109/08977194.2011.585609

Cited by 8 publications

(6 citation statements)

References 118 publications

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“…HGF, originally purified as a potent mitogen for hepatocytes, has anti-apoptotic activities in various cells including cardiac myocytes 20 21 22 23 . Administration of recombinant HGF protein in rats reduced infarct area size and improved cardiac function by suppressing apoptosis in cardiac myocytes 24 .…”

Section: Discussionmentioning

confidence: 99%

Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion

Yamaguchi

Shibata

Yamamoto

et al. 2015

Sci Rep

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Stem cells from human exfoliated deciduous teeth (SHEDs) can regenerate various tissues. We investigated the impact of SHED-conditioned medium (SHED-CM) on myocardial injury in a mouse model of ischemia-reperfusion (I/R). Wild-type (WT) mice were subjected to myocardial ischemia followed by reperfusion. SHED-CM was intravenously injected at 5 min after reperfusion. Administration of SHED-CM reduced myocardial infarct size as well as decreased apoptosis and inflammatory cytokine levels, such as TNF-α, IL-6, and IL-β, in the myocardium following I/R. In cultured cardiac myocytes, SHED-CM significantly suppressed apoptosis under hypoxia/serum-deprivation and reduced LPS-induced expression of pro-inflammatory genes. Furthermore, anti-apoptotic action of SHED-CM was stronger than bone marrow-derived stem cell (BMSC)-CM or adipose-derived stem cell (ADSC)-CM in cardiac myocytes. SHED-CM contains a higher concentration of hepatocyte growth factor (HGF) than BMSC-CM and ADSC-CM, and neutralization of HGF attenuated the inhibitory actions of SHED-CM on apoptosis in cardiac myocytes. Finally, WT mice were intravenously treated with an HGF-depleted SHED-CM, followed by myocardial I/R. HGF depletion significantly attenuated the inhibitory actions of SHED-CM on myocardial infarct size and apoptosis after I/R. SHED-CM protects the heart from acute ischemic injury because it suppresses inflammation and apoptosis. SHED-CM could be a useful treatment option for acute myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion

Yamaguchi

Shibata

Yamamoto

et al. 2015

Sci Rep

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“…To date, c-Met has been well-established as playing critical roles in growth, motility, migration and invasion [28,29]. c-Met has also been found to be aberrantly activated in human cancers via mutation, amplification or protein overexpression [30].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-409-3p Functions as a Tumor Suppressor in Human Lung Adenocarcinoma by Targeting c-Met

Wan

Zhu²,

Xu³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Dysregulation of microRNAs is correlated with tumor development. The aim of this study is to investigate the clinicopathologic and prognostic significance of microRNA (miR)-409-3p and its tumor suppressor roles in lung adenocarcinoma (LAD). Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect miR-409-3p expression in LAD tissues and corresponding noncancerous tissues. Additionally, the correlations of miR-409-3p expression with clinicopathologic factors and prognosis of patients were statistically analyzed. Next, we investigated whether miR-409-3p could function as a tumor suppressor in LAD cells via regulation of Akt signaling by targeting receptor tyrosine kinase (c-Met). Results: MiR-409-3p was significantly downregulated in LAD tissues compared with corresponding noncancerous tissues. Low miR-409-3p expression was observed to be significantly correlated with poorer tumor differentiation, advanced pTNM stage and higher incidence of lymph node metastasis. Multivariate Cox regression analyses showed that miR-409-3p expression was an independent prognostic factor for LAD patients. Functional analyses indicated that miR-409-3p could inhibit growth, induce apoptosis, reduce migration and invasion in LAD cells via inactivation of Akt signaling by targeting c-Met. Conclusions: MiR-409-3p was an independent prognostic factor and functioned as a tumor suppressor in LAD via regulation of Akt signaling by targeting c-Met.

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“…Furthermore, the ability of c‐met to stimulate lumen formation was dose‐dependent in treatment with HGF in vitro . However, paradoxical intracellular signalling activated by HGF/c‐met included PI3K/AKT and Ras/ERK1/2 contributing to mitogenic and prosurvival effects with also Fas/caspase 8/caspase 3 inducing apoptosis . Additionally, some differences of amino acids at hairpin loop and K1 domain in α chain and β chain which were essential for HGF/c‐met signalling were noticed between human and dog .…”

Section: Discussionmentioning

confidence: 99%

“…24 However, paradoxical intracellular signalling activated by HGF/c-met included PI3K/AKT and Ras/ERK1/2 contributing to mitogenic and prosurvival effects with also Fas/caspase 8/caspase 3 inducing apoptosis. 25 Additionally, some differences of amino acids at hairpin loop and K1 domain in α chain and β chain which were essential for HGF/c-met signalling were noticed between human and dog. 26 So far, the biological functions elicited by canine HGF/c-met signal in expression of c-met was detected in oestrogen receptor and human epidermal growth factor receptor 2 (HER 2) positive human breast cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic value of c‐met in canine mammary tumours

Chen

Liao

et al. 2018

Vet Comparative Oncology

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C-met is a receptor normally expressed on epithelial cells and dysregulated in human breast cancers. Mammary tumours are the most common tumour in female dogs. The aims of this study were to detect the expression of c-met in canine mammary tumours (CMTs) and evaluate the correlations between c-met expression and clinicopathological features. A total of 240 specimens of canine mammary tissues composed of 30 normal glands, 30 hyperplastic ones, 90 benign tumours and 90 carcinomas obtained from 127 bitches were examined by immunohistochemical staining. Positive c-met immunoreactivity was demonstrated in the cytoplasm of mammary epithelial cells at variable levels, and in malignant CMTs, higher c-met expression was found in carcinomas whose grade, stage and mitotic index were low, and metastasis was absent. The median survival time was shorter in dogs with malignant CMTs with a maximum diameter ≥5 cm, regional lymph node or distant metastasis, and a high histologic grade. However, the 2-year survival rate was higher in dogs with malignant CMTs of higher c-met expression than those of low c-met expression (80.1% vs 57%). C-met expression could be used as a valuable positive prognostic factor for the clinical outcomes of dogs with malignant CMTs.

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Paradoxical action of growth factors: antiproliferative and proapoptotic signaling by HGF/c-MET

Cited by 8 publications

References 118 publications

Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion

Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion

MicroRNA-409-3p Functions as a Tumor Suppressor in Human Lung Adenocarcinoma by Targeting c-Met

Expression and prognostic value of c‐met in canine mammary tumours

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