c-MET immunostaining in colorectal carcinoma is associated with local disease recurrence

Al-Maghrabi, Jaudah; Emam, Eman; Gomaa, Wafaey; Saggaf, Moaath M.; Buhmeida, Abdelbaset; Al-Ahwal, Mahmoud

doi:10.1186/s12885-015-1662-6

Cited by 48 publications

(40 citation statements)

References 23 publications

(23 reference statements)

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“…Furthermore, CSC is known as a pivotal factor contributing to cancer relapse and metastasis. Studies that show c‐Met activation is associated with poor prognosis for survival and local disease recurrence supports our findings (Al‐Maghrabi et al, ; Lee et al, ). Our results show that celecoxib suppresses CSC property of CRC cells mainly through c‐Met inhibition.…”

Section: Discussionsupporting

confidence: 91%

c‐Met inhibition is required for the celecoxib‐attenuated stemness property of human colorectal cancer cells

Lin

Hsiang

et al. 2018

Journal Cellular Physiology

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Cyclooxygenase‐2 (COX‐2) is frequently overexpressed and enhances colorectal cancer (CRC) tumorigenesis, including cancer stem cell (CSC) regulation. Accordingly, nonsteroidal anti‐inflammatory drugs (NSAIDs), inhibiting COX‐1/2 activity, are viewed as potential drugs for CRC treatment. Accumulated evidence indicates that celecoxib has the most potency for antitumor growth among NSAIDs and the underlying mechanism is only partly dependent on COX‐2 inhibition. However, the potency of these NSAIDs on CSC inhibition is still not known. In this study, we found that among these NSAIDs, celecoxib has the most potency for CSC inhibition of CRC cells, largely correlating to inhibition of c‐Met, not COX‐2. Further analysis reveals that c‐Met activity was required for basal CSC property. Silence of c‐Met blocked whereas overexpression of c‐Met enhanced the celecoxib‐inhibited CSC property. Collectively, these results not only first elucidate the mechanism underlying celecoxib‐inhibited CSC but also indicate c‐Met as a critical factor for the CSC property of CRC cells.

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Section: Discussionsupporting

confidence: 91%

c‐Met inhibition is required for the celecoxib‐attenuated stemness property of human colorectal cancer cells

Lin

Hsiang

et al. 2018

Journal Cellular Physiology

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“…A growing body of evidence‐based research shows that c‐Met tyrosine kinase inhibitors can block c‐Met signaling and reverse tumor growth in different cancers . Recent studies have shown that MET signaling in lung cancer and gastric cancer is sensitive to inhibition using a specific tyrosine kinase inhibitor . These findings suggested that overexpressed c‐Met may act as an important biomarker for CRC targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Role of HGF/c‐Met in the treatment of colorectal cancer with liver metastasis

Yao

Yan

et al. 2019

J Biochem & Molecular Tox

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The system of hepatocyte growth factor (HGF) and its receptor c‐Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c‐Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c‐Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c‐Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c‐Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c‐Met expression with tumor stages of CRC liver metastasis, as well as c‐Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c‐Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c‐Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.

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“…[181920] Two cylindrical cores of 1.5 mm in diameter were selected from donor paraffin blocks and arrayed in recipient paraffin blocks using the automated tissue arrayer (Master 3D Histech). Normal placenta tissue was used as control tissue to help orientation of samples in each tissue microarray block.…”

Section: Methodsmentioning

confidence: 99%

p16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma

Al-Ahwal¹,

Gomaa²,

Emam³

et al. 2016

Saudi J Gastroenterol

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Background/Aims:p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC).Patients and Methods:Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed.Results:Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325).Conclusion:Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target.

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c-MET immunostaining in colorectal carcinoma is associated with local disease recurrence

Cited by 48 publications

References 23 publications

c‐Met inhibition is required for the celecoxib‐attenuated stemness property of human colorectal cancer cells

c‐Met inhibition is required for the celecoxib‐attenuated stemness property of human colorectal cancer cells

Role of HGF/c‐Met in the treatment of colorectal cancer with liver metastasis

p16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma

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