Correlation between HGF/c-Met and Notch1 signaling pathways in human gastric cancer cells

Huang, Kai; Do, Sung I; Fang, Wen-Liang; Chi, Chin‐Wen; Yeh, Ta‐Sen; Yin, Pen-Hui; Li, Anna Fen–Yau; Wu, Chew-Wun; Shyr, Yi‐Ming; Yang, Muh‐Hwa

doi:10.3892/or.2018.6447

Cited by 21 publications

(16 citation statements)

References 29 publications

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“…Data from subgroup analysis related to method, race, tumor stage and type of aberration (amplification or expression) suggested that elevated MET expression had a significant negative impact on survival [73,74]. More recent published reports have confirmed these earlier findings [52,86,103,104].…”

Section: Ii-a-4-gastric Cancermentioning

confidence: 79%

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Moosavi

Giovannetti

Saso³

et al. 2019

Critical Reviews in Clinical Laboratory Sciences

125

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Cancer is a major cause of death worldwide. MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer. The HGF/MET pathway has emerged as an important actionable target across many solid tumors; therefore, biomarker discovery becomes essential in order to guide clinical intervention and patient stratification with the aim of moving towards personalized medicine. The focus of this review is on how the aberrant activation of the HGF/MET pathway in tumor tissue or the circulation can provide diagnostic and prognostic biomarkers and predictive biomarkers of drug response. Many meta-analyses have shown that aberrant activation of the MET pathway in tumor tissue, including MET gene overexpression, gene amplification, exon 14 skipping and other activating mutations, is almost invariably associated with shorter survival and poor prognosis. Most meta-analyses have been performed in non-small cell lung cancer (NSCLC), breast, head and neck cancers as well as colorectal, gastric, pancreatic and other gastrointestinal cancers. Furthermore, several studies have shown the predictive value of MET biomarkers in the identification of patients who gain the most benefit from HGF/MET targeted therapies administered as single or combination therapies. The highest predictive values have been observed for response to foretinib and savolitinib in renal cancer, as well as tivantinib in NSCLC and colorectal cancer. However, some studies, especially those based on MET expression, have failed to show much value in these stratifications. This may be rooted in lack of standardization of methodologies, in particular in scoring systems applied in immunohistochemistry determinations or absence of oncogenic addiction of cancer cells to the MET pathway, despite detection of overexpression. Measurements of amplification and mutation aberrations are less likely to suffer from these pitfalls. Increased levels of MET soluble ectodomain (sMET) in circulation have also been associated with poor prognosis; however, the evidence is not as strong as it is with tissue-based biomarkers. As a diagnostic biomarker, sMET has shown its value in distinguishing cancer patients from healthy individuals in prostate and bladder cancers and in melanoma. On the other hand, increased circulating HGF has also been presented as a valuable prognostic and diagnostic biomarker in many cancers; however, there is controversy on the predictive value of HGF as a biomarker. Other biomarkers such as circulating tumor DNA (ctDNA) and tumor HGF levels have also been briefly covered. In conclusion, HGF/MET aberrations can provide valuable diagnostic, prognostic and predictive biomarkers and represent vital assets for personalized cancer therapy.

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Section: Ii-a-4-gastric Cancermentioning

confidence: 79%

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Moosavi

Giovannetti

Saso³

et al. 2019

Critical Reviews in Clinical Laboratory Sciences

125

View full text Add to dashboard Cite

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“…The promotion of astrocyte de‐differentiation by MSC was associated with a reduced expression of the Notch target gene Hes1 , suggesting that soluble factors released by MSC may impair activation of Notch pathway in astrocytes, thereby favoring neural stem cell activities (Magnusson et al, 2014). In this context, a negative feedback loop was recently demonstrated between hepatocyte growth factor (HGF), a soluble mediator of the remyelinating effect of MSC in EAE (Bai et al, 2012), and Notch pathway (Huang et al, 2018), suggesting that MSC could promote de‐differentiation of reactive astrocytes through the HGF‐dependent inhibition of Notch signaling in astrocytes. Accordingly, inhibition of Notch pathway has been demonstrated to alleviate EAE and promote remyelination (Bassil et al, 2011; Hammond et al, 2014), thus pointing to Notch as a possible candidate pathway for the implication of MSC in therapeutic modulation of astrocyte properties.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells instruct a beneficial phenotype in reactive astrocytes

Vigo

Voulgari-Kokota

Errede

et al. 2020

Glia

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Transplanted mesenchymal stromal/stem cells (MSC) ameliorate the clinical course of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), reducing inflammation and demyelination. These effects are mediated by instructive cross‐talk between MSC and immune and neural cells. Astroglial reaction to injury is a prominent feature of both EAE and MS. Astrocytes constitute a relevant target to control disease onset and progression and, based on their potential to acquire stem cell properties in situ, to foster recovery in the post‐acute phase of pathology. We have assessed how MSC impact astrocytes in vitro and ex vivo in EAE. Expression of astroglial factors implicated in EAE pathogenesis was quantified by real‐time PCR in astrocytes co‐cultured with MSC or isolated from EAE cerebral cortex; astrocyte morphology and expression of activation markers were analyzed by confocal microscopy. The acquisition of neural stem cell properties by astrocytes was evaluated by neurosphere assay. Our study shows that MSC prevented astrogliosis, reduced mRNA expression of inflammatory cytokines that sustain immune cell infiltration in EAE, as well as protein expression of endothelin‐1, an astrocyte‐derived factor that inhibits remyelination and contributes to neurodegeneration and disease progression in MS. Moreover, our data reveal that MSC promoted the acquisition of progenitor traits by astrocytes. These data indicate that MSC attenuate detrimental features of reactive astroglia and, based on the reacquisition of stem cell properties, also suggest that astrocytes may be empowered in their protective and reparative actions by MSC.

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“…It can be concluded that COX-2 and Notch knockdown or inhibitors may play a role in the therapeutic strategy against HGF/ c-MET pathway. 37,38 Targeted Therapy Against MET Pathway in GC…”

Section: -Kinase (Pi3k)/akt Extracellular Signal-regulated Kinase (Ementioning

confidence: 99%

<p><em>MET</em> Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential?</p>

Darsa¹,

Sayed²,

Abdel‐Rahman³

2020

JEP

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Gastric cancer remains a disease with a dismal prognosis. Extensive efforts to find targetable disease drivers in gastric cancer were implemented to improve patient outcomes. Beyond anti-HER2 therapy, MET pathway seems to be culprit of cancer invasiveness with MET-overexpressing tumors having poorer prognosis. Tyrosine kinase inhibitors targeting the HGF/MET pathway were studied in MET-positive gastric cancer, but no substantial benefit was proven. Some patients responded in early phase trials but later developed resistance. Others failed to show any benefit at all. Etiologies of resistance may entail inappropriate patient selection with a lack of MET detection standardization, tumor alternative pathways, variable MET amplification, and genetic variation. Optimizing MET detection techniques and better understanding the MET pathway, as well as tumor bypass mechanisms, are an absolute need to devise means to overcome resistance using targeted therapy alone, or in combination with other synergistic agents to improve outcomes of patients with MET-positive GC.

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Correlation between HGF/c-Met and Notch1 signaling pathways in human gastric cancer cells

Cited by 21 publications

References 29 publications

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Mesenchymal stem cells instruct a beneficial phenotype in reactive astrocytes

<p><em>MET</em> Inhibitors for the Treatment of Gastric Cancer: What’s Their Potential?</p>

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