The Prognostic Significance of RON and MET Receptor Coexpression in Patients with Colorectal Cancer

Lee, Chung Ta; Chow, Nan Haw; Su, Pei Fang; Lin, Shao Chieh; Lin, Peng; Lee, Jenq Chang

doi:10.1007/s10350-008-9297-1

Cited by 60 publications

(65 citation statements)

References 31 publications

(43 reference statements)

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“…Patients with tumors coexpressing MET and MST1R reportedly have a worse prognosis than those with single receptor-positive tumors. 34,62,63 The synergistic effect of MET and MST1R might induce a favorable outcome, as MET expression is associated with a better prognosis in cHL.…”

Section: Discussionmentioning

confidence: 99%

MET and MST1R as prognostic factors for classical Hodgkin's lymphoma

et al. 2013

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MST1R (RON) and MET are receptor tyrosine kinase gene family members that form a noncovalent complex on the cell surface, a critical step in tumor progression. A recent study suggested a prognostic role of MET expression in Hodgkin/Reed-Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL). The purpose of this study was to examine the prognostic significance of MET and MST1R expression in cHL. The prognostic impact of MET and MST1R was examined in 100 patients with cHL (median age: 32 years) by immunohistochemistry and mRNA in situ hybridization. The median follow-up time was 95 months (interquartile range: 42-126 months). MET or MST1R protein expression was associated with high MET or MST1R mRNA expression, respectively. Thirty-eight patients (38%) expressed MET protein in HRS cell, which was associated with better overall survival (P ¼ 0.004). Twenty-six patients (26%) expressed MST1R protein, which was associated with better overall survival (P ¼ 0.022) and event-free survival (P ¼ 0.021). Multivariate analysis identified MET protein as an independent prognostic factor for overall survival and MST1R protein as an independent prognostic factor for event-free survival. Subgroup analysis according to Ann Arbor stage showed that expressions of MET and MST1R protein have prognostic impact in the advanced stage only. In particular, coexpression of MST1R and MET protein was associated with a better survival outcome than MET or MST1R expression alone or no expression. This study suggests that MET and MST1R are independent prognostic factors in classical cHL, and may allow the identification of a subgroup of cHL patients who require more intensive therapy.

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Section: Discussionmentioning

confidence: 99%

MET and MST1R as prognostic factors for classical Hodgkin's lymphoma

et al. 2013

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“…RON modulates diverse processes involved in tumor progression and metastasis in a variety of human cancers (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Consequently, an understanding of the molecular alterations of RON that facilitate tumor progression and metastasis will provide insight into approaches to optimized target therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Transgenic mouse models overexpressing RON in lung or mammary epithelial cells develop lung and breast carcinomas and are associated with metastatic dissemination (20,21). RON is overexpressed in a variety of human epithelial cancers including breast, colon, lung, ovary, pancreas and bladder (22)(23)(24)(25)(26)(27). Moreover, RON overexpression is associated with poor survival as well as metastasis in breast, colon and bladder cancers (22,23,27).…”

Section: Introductionmentioning

confidence: 99%

“…RON is overexpressed in a variety of human epithelial cancers including breast, colon, lung, ovary, pancreas and bladder (22)(23)(24)(25)(26)(27). Moreover, RON overexpression is associated with poor survival as well as metastasis in breast, colon and bladder cancers (22,23,27). Also, RON has been shown to be overexpressed at mRNA and protein levels in HCC (28).…”

Section: Introductionmentioning

confidence: 99%

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Small interfering RNA-directed targeting of RON alters invasive and oncogenic phenotypes of human hepatocellular carcinoma cells

Joo

2011

Oncol Rep

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Abstract. The recepteur d'origine nantais (RON) receptor tyrosine kinase is highly expressed in various cancers including human hepatocellular carcinoma (HCC) and involved in tumor progression. The aims of the current study were to evaluate whether RON affects tumor cell behavior and oncogenic signaling cascades in HCC cells. We investigated the biologic role of RON on tumor cell behavior and oncogenic signaling cascades including Akt, c-Raf and extracellular signal-regulated kinase (ERK) by using the small interfering RNA (siRNA) in HCC cell lines, chang, HepG2 and Huh7. Knockdown of RON suppressed tumor cell migration and invasion in all tested HCC cell lines. The proportion of apoptotic cells induced by knockdown of RON was greater than that induced by transfection of the scramble siRNA in all tested HCC cell lines. Knockdown of RON resulted in cell cycle arrest in the G 2 /M phase of chang and Huh7 cells, and sub G 1 phase of HepG2 cells. Knockdown of RON activated cleaved caspase-3 and PARP, and down-regulated the expression of Bcl-2, Bcl-xL and survivin, leading to induction of apoptosis in all tested cell lines. Knockdown of RON negatively regulates the progression of the cell cycle by decreasing cyclin D1 and D3, and increasing p21 and p27 in all tested cell lines. The phosphorylation of Akt, c-Raf and ERK1/2 signal proteins was significantly blocked by knockdown of RON in all tested cell lines. These results suggest that RON is associated with invasive and oncogenic phenotypes such as tumor cell migration, invasion, resistance to apoptosis and cell cycle arrest through the modulation of Akt, c-Raf and ERK signaling cascades in HCC cells.

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“…RON and Met concomitant overexpression is detected in many tumor types. 65,68 Lee et al 66 found that overexpression of RON and c-Met in CRC is associated with a remarkably poor clinical outcome and short-term disease-free survival. Various mechanisms underlay on abnormal expression and activation of c-Met and RON such as gene amplification, enhanced TK activity due to point mutations, and aberrant splicing of RON.…”

Section: C-met and Ron Receptorsmentioning

confidence: 99%

The c-Met receptor: Implication for targeted therapies in colorectal cancer

et al. 2017

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c-Met (mesenchymal-epithelial transition factor) is a tyrosine kinase receptor activated by hepatocyte growth factor and regulates multiple biological processes, such as cell scattering, survival, and proliferation. Aberrant c-Met signaling has been implicated in a variety of cancer types, including colorectal cancer. c-Met is genetically altered through various mechanisms that is associated with colorectal cancer progression and metastasis. Especially, in colorectal cancer, preclinical evidence for the aberrant activation of the c-Met signaling exists. Accordingly, molecular targeting of c-Met receptor could be a promising strategy, in the treatment of colorectal cancer patients. Recently, it was also shown that crosstalk between c-Met and other cell surface receptors attributes to tumorigenesis and development of therapeutic resistance. Characterization of the molecular mechanisms through which c-Met crosstalks with other receptors in favor of tumor formation and progression remains to explore. This review will describe the mechanisms of aberrant c-Met signaling in colorectal cancer and discuss on additional roles for c-Met receptor through crosstalk with other tyrosine kinase receptors and cell surface proteins in colorectal cancer. Novel therapeutic approaches for c-Met pathway targeting will also be discussed.

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The Prognostic Significance of RON and MET Receptor Coexpression in Patients with Colorectal Cancer

Abstract: The crosstalk between RON and MET in colorectal cancer seems important. Evaluating the expression patterns of RON and MET was predictive of clinical outcome for patients with colorectal cancer.

Cited by 60 publications

References 31 publications

MET and MST1R as prognostic factors for classical Hodgkin's lymphoma

MET and MST1R as prognostic factors for classical Hodgkin's lymphoma

Small interfering RNA-directed targeting of RON alters invasive and oncogenic phenotypes of human hepatocellular carcinoma cells

The c-Met receptor: Implication for targeted therapies in colorectal cancer

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