RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells

Yin, Binbin; Liu, Zhenping; Wang, Yiyun; Wang, Xuchu; Liu, Weiwei; Pan, Yu; Duan, Xin; Liu, Chunhua; Chen, Yuhua; Zhang, Yurong; Pan, Xiaoyan; Yao, Hang‐Ping; Liao, Zhaoping; Tao, Zhihua

doi:10.3892/or.2017.5585

Cited by 30 publications

(31 citation statements)

References 25 publications

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“…The concentrations of serum HGF measured by Nagakawa et al turned out to be higher than in our study, but the relationship remains similar. The study by Yin et al shows increased expression of c-Met , the HGF receptor in prostate cancer cells in vitro, in metastatic-dependent manner [ 76 ]. It allows to use HGF as a potential indirect prostate cancer biomarker.…”

Section: Discussionmentioning

confidence: 99%

Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance with PSA Marker in Prostate Cancer

Fryczkowski¹,

Bułdak

Hejmo

et al. 2018

Disease Markers

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Background Prostate cancer (PCa) is the first in terms of occurrence in Europe and second in Poland. The PCa risk factors include: genetic load, obesity, diet rich in fat, hypertriglyceridemia, and exposure to androgens. The prostate-specific antigen (PSA) level may be elevated in prostate cancer or other prostate disorders. Fat tissue secretes adipocytokines, which increase the risk of cancer development and metastasis. Objectives The aims of the study were to investigate the relationship between circulating levels of PSA, adipocytokines: omentin, leptin, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in serum obtained from patients with benign prostate hyperplasia (BPH) and prostate cancer (PCa). Methods Forty patients diagnosed with BPH and forty diagnosed with PCa were assessed for the purpose of the study. The concentrations of omentin, leptin, HGF, and VEGF were determined using enzyme-linked immunosorbent assays (EIA). Results PSA level was significantly higher in the PCa group than in BPH (18.2 versus 9 ng/mL, p < 0.01), while volume of prostate gland was significantly higher in the BPH group than in PCa (39.1 versus 31.1 cm3, p = 0.02). HGF, VEGF, omentin, and leptin concentrations were significantly higher in PCa group than in BPH (359.5 versus 294.9 pg/mL, p = 0.04; 179.3 versus 127.3 pg/mL, p < 0.01; 478.8 versus 408.3 ng/mL, p = 0.01; 15.7 versus 11.2 ng/mL, p = 0.02, resp.). The multiple logistic regression analysis demonstrated that only omentin and PSA levels were independent predictors of PCa in studied subjects. Conclusions PSA level as well as the level of omentin may be valuable markers of PCa with clinical significance, when compared to PSA.

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Section: Discussionmentioning

confidence: 99%

Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance with PSA Marker in Prostate Cancer

Fryczkowski¹,

Bułdak

Hejmo

et al. 2018

Disease Markers

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“…It was suggested that IBC inhibited the invasion of Tca8113 cells by downregulating MMP-2 and MMP-9 protein expression. Previous studies have demonstrated that abnormal activation of ERK/p-ERK is able to activate a series of cytoplasmic proteins to promote the invasion and metastasis of cancer cells ( 25 , 26 ). In addition, the Akt signaling pathway also served a role in the expression of MMP-2 and MMP-9 proteins ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Isobavachalcone inhibits the proliferation and invasion of tongue squamous cell carcinoma cells

Shi¹,

Wu²,

Huo³

et al. 2017

Oncology Letters

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Isobavachalcone (2′,4′,4-trihydroxy-3′-[3′-methylbut-3′-ethyl] chalcone or IBC) exhibits anticancer activities in a number of types of cancer cell. However, its role in tongue squamous cell carcinoma (TSCC) cells remains unclear. The aim of the present study was to investigate the biological effect of IBC in TSCC Tca8113 cells. The function of IBC on Tca8113 cell apoptosis and apoptosis-associated signaling pathways was determined using an MTT assay, morphological staining, annexin V-propidium iodide (PI) staining and Western blot analysis. The effects of IBC on Tca8113 cell migration, invasion and relative protein expression were confirmed using wound healing analysis, Transwell invasion analysis and Western blot analysis, respectively. The results of the MTT assay and annexin V-PI staining indicated that IBC is able to significantly inhibit proliferation and induce apoptosis of Tca8113 cells in vitro. IBC treatment resulted in typical apoptotic morphology of nuclear fragmentation and apoptotic bodies in Tca8113 cells. Western blot analysis further demonstrated that IBC caused downregulation of the expression of B-cell lymphoma 2 (Bcl-2) protein, upregulation of the expression of Bcl-2-associated X protein (Bax), activation of caspases, and dephosphorylation of protein kinase B (Akt) and extracellular-signal-regulated kinase (ERK) proteins in a concentration- and time-dependent manner. The results of the present study suggest that IBC induces apoptosis in Tca8113 cells and that the induction may be associated with the activation of Bcl-2, Bax and caspase-3, and the inactivation of Akt and ERK. Furthermore, IBC inhibited migration and invasion of Tca8113 cells in vitro by downregulating matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. The results of the present study indicate that IBC may be a potential anticancer drug for the treatment of TSCC.

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“…SEMA is the site where HGF binds directly to c-Met, and PSI can stabilize this interaction. Ser-975 and Tyr-1003 sites at the juxtamembrane domain play an important role in the negative regulation of c-Met [ 14 , 22 , 23 ]. When HGF binds c-Met, Tyr-1234 and Tyr-1235 in the intracellular tyrosine kinase domain undergo autophosphorylation, which results in autophosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal docking site.…”

Section: Structures Of C-met and Hgfmentioning

confidence: 99%

“…The most common grade 3 and higher toxic adverse reactions were mainly high blood pressure, diarrhea, nausea, and fatigue. Yin et al [ 22 ] also demonstrated that foretinib inhibits prostate cancer (PCa) metastasis by targeting c-Met.…”

Section: Current Clinical Trials Targeting C-metmentioning

confidence: 99%

Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities

et al. 2018

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c-Met is a receptor tyrosine kinase belonging to the MET (MNNG HOS transforming gene) family, and is expressed on the surfaces of various cells. Hepatocyte growth factor (HGF) is the ligand for this receptor. The binding of HGF to c-Met initiates a series of intracellular signals that mediate embryogenesis and wound healing in normal cells. However, in cancer cells, aberrant HGF/c-Met axis activation, which is closely related to c-Met gene mutations, overexpression, and amplification, promotes tumor development and progression by stimulating the PI3K/AKT, Ras/MAPK, JAK/STAT, SRC, Wnt/β-catenin, and other signaling pathways. Thus, c-Met and its associated signaling pathways are clinically important therapeutic targets. In this review, we elaborate on the molecular structure of c-Met and HGF and the mechanism through which their interaction activates the PI3K/AKT, Ras/MAPK, and Wnt signaling pathways. We also summarize the connection between c-Met and RON and EGFR, which are also receptor tyrosine kinases. Finally, we introduce the current therapeutic drugs that target c-Met in primary tumors, and their use in clinical research.

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RON and c-Met facilitate metastasis through the ERK signaling pathway in prostate cancer cells

Cited by 30 publications

References 25 publications

Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance with PSA Marker in Prostate Cancer

Circulating Levels of Omentin, Leptin, VEGF, and HGF and Their Clinical Relevance with PSA Marker in Prostate Cancer

Isobavachalcone inhibits the proliferation and invasion of tongue squamous cell carcinoma cells

Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities

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