Inhibition of HGF/cMET expression prevents distant recurrence of rectal cancer after preoperative chemoradiotherapy

Saigusa, Susumu; Toiyama, Yuji; Yokoe, Takeshi; Fujikawa, Hiroyuki; Matsushita, Kohei; Okugawa, Yoshinaga; Inoue, Yasuhiro; Uchida, Keiji; Mohri, Yasuhiko; Kusunoki, Masato

doi:10.3892/ijo.2011.1200

Cited by 15 publications

(17 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The subsequent production of cMET and the activation of its related pathway eventually boost the incidence of local and distant recurrence. In this regard, the inhibition of the HGF/cMET pathway may, therefore, represent a valid therapeutic approach for rectal cancer patients treated with preoperative chemoradiation, as it could potentially improve outcome by decreasing radiation-induced HGF up-regulation and metastatic potential [71]. …”

Section: Cmet As Prognostic Biomarkermentioning

confidence: 99%

Role of cMET in the Development and Progression of Colorectal Cancer

Pérez-Vargas

Biondani

Maggi

et al. 2013

IJMS

View full text Add to dashboard Cite

Mesenchymal-epithelial transition (MET) is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF). Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC), by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies.

show abstract

Section: Cmet As Prognostic Biomarkermentioning

confidence: 99%

Role of cMET in the Development and Progression of Colorectal Cancer

Pérez-Vargas

Biondani

Maggi

et al. 2013

IJMS

View full text Add to dashboard Cite

show abstract

“…When the antagonist Nk4 was used to inhibit the ability of HGF in colon cancer cells, metastasis decreased in animal models7. Inhibition of HGF and Met was reported to prevent distant metastasis for rectal cancer after preoperative chemoradiotherapy8. In clinical reports, Met amplification and overexpression at the levels of DNA, RNA and protein were observed in colonic adenomas, primary tumors and liver metastases while less expression existed in normal colonic tissues2,3,9.…”

Section: Introductionmentioning

confidence: 99%

“…Their expression in primary tumors was associated with colorectal cancer metastasis and has been used to evaluate prognosis and metastasis of colorectal cancer2-4,6,12-18. At the treatment levels, the inhibitors of HGF/Met are being developed to be novel targeted drugs19,20 for controlling colorectal cancer metastasis8,21.…”

Section: Introductionmentioning

confidence: 99%

Expression of HGF and Met in Human Tissues of Colorectal Cancers: Biological and Clinical Implications for Synchronous Liver Metastasis

Sun¹,

Liu²,

Ma³

et al. 2013

Int. J. Med. Sci.

View full text Add to dashboard Cite

Background and aims: Synchronous liver metastasis (SLM) remains a significant problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte growth factor (HGF) and Met plays an important role in cancer invasion and metastasis and is being developed to be targeted drugs. We aimed to investigate the role of HGF/Met in SLM based on a case-matched study and comparison between primary tumors and matched metastases.Methods: A group of 30 patients with SLM and other two groups of patients without SLM in a hospital database were collected. They were matched into according to clinicopathological factors. 81 patients were included in the study. Their tissues of primary colorectal cancers, lymph nodes and liver metastases were collected to detect HGF and Met expression by immunohistochemistry and RT-PCR.Results: Expression of HGF and Met at the protein level and the RNA level in primary CRCs with SLM were significantly higher than that in primary colorectal carcinomas without liver metastases (all P value<0.05). Their expression was only related to SLM when concurrent with regional lymph node metastasis (all P value<0.05) but had little influence on SLM without involvement of lymph node metastasis (all P value>0.05). Comparison their expression between primary tumors and matched metastases, major concordance and minor difference existed.Conclusions: HGF and Met may exert functions in the development of SLM when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, further indicating their roles and potential values for a subtype of colorectal cancer metastasis. Major concordance and minor difference exist between primary tumors and matched metastases, which further provides evidence for evaluating the response to their inhibitors based on primary tumors or metastases.

show abstract

“…Fifth, abnormality in RON expression contributes to the acquired resistance to conventional chemoagents. Therefore, various strategies have been reported to block the c-MET/RON pathways for targeted cancer treatment (42)(43)(44)(45). Aberrant RON expression is featured by generation of biologically active RON variants (46).…”

Section: Comparative Proteomics Of Ron Proteins Identified In Vertebrmentioning

confidence: 99%

Integrative genomic analyses of recepteur d’origine nantais and its prognostic value in cancer

Yuan

Chu

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Recepteur d'origine nantais (RON) is a receptor tyrosine kinase (RTK) normally expressed at low levels in epithelial cells. RON is a 180-kDa heterodimeric protein composed of a 40-kDa α-chain and a 150-kDa transmembrane β-chain with intrinsic tyrosine kinase activity. The extracellular sequences of RON contain several domains including an N-terminal semaphorin (sema) domain, followed by the plexin, semaphorin, integrin (PSI) domain, and four immunoglobulin, plexin, transcription factor (IPT) domains. Here, we identified RON genes from 14 vertebrate genomes and found that RON exists in all types of vertebrates including fish, amphibians, birds and mammals. We found that the human RON gene showed predominant expression in the liver, lymph node, thymus, intestine, lung, mammary gland, bone marrow, brain, heart, placenta, bladder, cortex, cervix, skin, kidney and prostate. When searched in the PrognoScan database, human RON was also found to be expressed in bladder, blood, breast, glioma, esophageal, colorectal, head and neck, ovarian, lung and skin cancer. The relationship between the expression of RON and prognosis was found to vary in different cancer types, even in the same cancer from different databases. This suggests that the function of RON in these tumors may be multidimensional, not just as a tumor suppressor or oncogene. Six available single-nucleotide polymorphisms (SNPs) disrupting existing exonic splicing enhancers were identified in RON. This may contribute to the generation of active RON variants by alternative splicing, which is frequently observed in primary tumors.

show abstract

Inhibition of HGF/cMET expression prevents distant recurrence of rectal cancer after preoperative chemoradiotherapy

Cited by 15 publications

References 32 publications

Role of cMET in the Development and Progression of Colorectal Cancer

Role of cMET in the Development and Progression of Colorectal Cancer

Expression of HGF and Met in Human Tissues of Colorectal Cancers: Biological and Clinical Implications for Synchronous Liver Metastasis

Integrative genomic analyses of recepteur d’origine nantais and its prognostic value in cancer

Contact Info

Product

Resources

About