The Role of HGF/c-Met Pathway Signaling in Human Medulloblastoma

Faria, Cláudia C.; Smith, Christian A.; Rutka, James T.

doi:10.5772/23296

Cited by 5 publications

(7 citation statements)

References 101 publications

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“…Human cells overexpressing either HGF and/or Met became tumorogenic. Similarly, the downregulation of HGF or Met expression in human tumor xenografts suppressed tumor growth (Faria et al, 2011). Gao et al reported the inhibition of anchorage‐dependent and independent growth of hepatocarcinoma cells and as well as HGF‐ induced c‐Met signaling pathway after treatment with resveratrol.…”

Section: Flavonoids In the Chemoprevention And Treatment Of Hepatocellular Carcinomamentioning

confidence: 99%

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

et al. 2021

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Chemopreventive approaches with food‐derived phytochemicals are progressively rising as a significant aspect of tumor management and control. Herein, we have showcased the major phytoconstituents belonging to the group of flavanoid, as anti‐cancer agents used for the treatment and prevention of hepatocellular carcinoma (HCC). Sorafenib is the sole drug used for the treatment of advanced HCC, but its clinical application is limited because of its severe adverse effects and drug resistance. Diet‐based chemoprevention seems to be the way forward for this disease of malignant nature. As HCC is derived from a chronic inflammatory milieu, the regular incorporation of bioactive phytochemicals in the diet will confer protection and prevent progression to hepatocarcinogenesis. Many preclinical studies proved that the health benefits of flavonoids confer cytotoxic potential against various types of cancers including hepatocellular carcinoma. As flavonoids with excellent safety profile are abundantly present in common vegetables and fruits, they can be better utilized for chemoprevention and chemosensitization in such chronic condition. This review highlights the plausible role of the eight most promising flavonoids (Curcumin, Kaempferol, Resveratrol, Quercetin, Silibinin, Baicalein, Galangin and Luteolin) as key orchestrators of chemoprevention in hepatocellular carcinoma with preclinical and clinical evidence. An attempt to address the challenges in its clinical translation is also included. This review also provides an insight into the close association of HCC and metabolic disorders which may further decipher the chemopreventive effect of dietary bioactive from a proof of concept to extensive clinical translation. Practical applications According to GLOBOCAN 2020 database, it is estimated that 905,677 new cases of liver cancer and approximately 830,180 deaths related to that. The cancer incidence and mortality are almost similar as it is diagnosed at an advanced stage in patients where systemic drug therapy is the sole approach. Due to the emergence of multidrug resistance and drug‐related toxicities, most of the patient can not adhere to the therapy regimen. Flavonoids are known to be a potential anticancer agent with an excellent safety profile. These are found to be effective preclinically against hepatocellular carcinoma through modulation of numerous pathways in hepatocarcinogenesis. But, the bioavailability issue, lack of well designed‐validated clinical evidence, the possibility of food–drug interaction etc limit its clinical utility. The research inputs mainly to overcome pharmacokinetic issues along with suitable validation of efficacy and toxicity will be a critical point for establishing flavonoids as an effective, safe, affordable therapeutics.

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Section: Flavonoids In the Chemoprevention And Treatment Of Hepatocellular Carcinomamentioning

confidence: 99%

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

et al. 2021

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“…It has also been shown that HGF regulates proliferation rates via signalling through SHP2, a protein tyrosine phosphatase that mediates MAPK activity; these proliferation rates were dependent on the HGF dose utilized (Chazaud, 2010;Li et al, 2009). MAPKs are thought to be more intensively involved in regulating cell proliferation, differentiation and cell migration, while signaling through PI3K mediates cell survival and resistance to apoptosis (Faria et al, 2011;Keren et al, 2005;Knight & Kothary, 2011;Li et al, 2000;Lluis et al, 2006;.…”

Section: Introductionmentioning

confidence: 97%

“…The phosphorylated residues become docking sites for a range of adaptor proteins including phosphatidylinositol-3-kinase (PI3K), Grb2-associated adaptor protein (Gab1) and growth factor receptor-bound protein 2 (Grb2). These pathways proceed to mediate c-Met-dependent cell proliferation, migration, survival, and differentiation (Faria et al, 2011). Grb2 and GAB transduce signals through mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinases (ERK1 and ERK2), Jun amino-terminal kinases (JNK1, JNK2, and JNK3), and p38.…”

Section: Introductionmentioning

confidence: 99%

Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways

et al. 2015

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Hepatocyte growth factor (HGF) regulates satellite cell activation, proliferation, and differentiation. We analyzed the dose-dependent effects of HGF on myogenesis. Murine C2C12 and human donor-derived skeletal muscle myoblasts were treated with 0, 2, or 10 ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2 ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10 ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly decreased expression in differentiating cells cultured with 2 ng/ml HGF, but increased expression in proliferating cells with 10 ng/ml HGF. Mitogen-activated protein kinase (MAPKs: ERK, JNK, or p38K) and phosphatidylinositol-3-kinase (PI3K) inhibition abrogated the HGF-stimulated increase in cell number. Interestingly, PI3K and p38 kinase facilitated the negative effect of HGF on proliferation, while ERK inhibition abrogated the HGF-mediated decrease in differentiation. Dose-dependent effects of HGF are mediated by changes in c-Met expression and downstream MAPK and PI3K signalling.

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“…The activation of c-Met can trigger the signal transduction of MAPK signal pathway, initiating cell proliferation and migration [31]. ERK1/2 are key members of MAPK family.…”

Section: Resultsmentioning

confidence: 99%

PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells

Yao²,

Zhu

et al. 2016

Oncotarget

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Previous studies showed that type II cGMP-dependent protein kinase G (PKG II) could inhibit the activation of epidermal growth factor receptor (EGFR). Both c-Met and EGFR belong to family of receptor tyrosine kinases (RTKs) and have high molecular analogy. However, the effect of PKG II on c-Met activation is unclear. This study was designed to investigate the inhibitory effect of PKG II on the activation of c-Met and consequent biological activities. The results from CCK8 assay, Transwell assay and TUNEL assay showed that HGF enhanced cell proliferation and migration, and decreased cell apoptosis. Activated PKG II reversed the above changes caused by HGF. Immunoprecipitation and Western blotting results showed that PKG II could bind with c-Met and phosphorylate its Ser985, and thereby inhibited HGF-induced activation of c-Met and MAPK/ERK and PI3K/Akt/mTOR mediated signal transduction. When Ser985 of c-Met was mutated to Alanine for preventing phosphorylation of this site, the blocking effect of PKG II on c-Met activation was annulled. When Ser985 of c-Met was mutated to Aspartic acid for mimicking phosphorylation of this site, HGF-induced activation of c-Met was prevented. In conclusion, the results indicated that PKG II could block c-Met activation via phosphorylating Ser985 of this RTK.

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The Role of HGF/c-Met Pathway Signaling in Human Medulloblastoma

Cited by 5 publications

References 101 publications

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways

PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells

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