Glial cell‐derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF‐κB pathways

Su, Chen; Lu, Dah Yuu; Chen, Hsien Te; Huang, Chuyi; Yang, Wei; Su, Yi; Yang, Shu Ning; Fong, Yi Chin; Tseng, Wen-Pei; Tang, Chih Hsin

doi:10.1002/jcp.21802

Cited by 34 publications

(32 citation statements)

References 34 publications

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“…Recently, our and other reports have shown that NF-kB signaling pathway play a key role of cancer cell motility in response to growth factors and adipokines [Huang et al, 2007;Su et al, 2009;Tan et al, 2009;Tang and Lu, 2009; Lu et al, 2010a,b]. The results of this study showed that NF-kB activation contributes to ghrelin-induced glioma cell migration, and that the inhibitors of the NF-kB dependent signaling pathway.…”

Section: Ghrelin Induces Migration In Glioma Cellssupporting

confidence: 51%

Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-κB signaling pathway in glioma cells

Chen¹,

Huang

Chen

et al. 2011

J. Cell. Biochem.

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Ghrelin is a newly discovered gastric peptide which stimulates food intake, energy balance, and growth hormone release. Recent reports have also shown that circulating ghrelin can efficiently reach the brain. However, the molecular mechanisms and pathophysiologic roles underlying ghrelin-induced glioma migration remain unclear. Glioma is the most common primary adult brain tumor with poor prognosis because of the spreading of tumor cell to the other regions of brain easily. In present study, we found that application of recombinant human ghrelin enhances the glioma cell migration in both rat C6 and human U251 cells. Ghrelin and its receptor GHS-R (growth hormone secretagogue receptor) are expressed in a wide variety of tissues and cell types, including various cancer cells. However, little is known about the expression of ghrelin or GHS-R in brain tumors. Here, we found that ghrelin increased GHS-R receptor up-regulation, and the enhancement of ghrelin-induced glioma cell motility markedly inhibited by a GHS-R antagonist. In addition, ghrelin-mediated migration was attenuated by treatment of CaMKII inhibitor, and AMPK inhibitors and pre-transfection with AMPK siRNA. Moreover, ghrelin stimulation also increased the phosphorylation of CaMKII and AMPK. Treatment with three different types of NF-κB inhibitors or pre-transfection with KM-IKKα, or KM-IKKβ also reduced ghrelin-induced glioma cell migration. Moreover, treatment of ghrelin also induced IKKα/β activation, IκBα phosphorylation, p65 phosphorylation at Ser(536), and increased NF-κB-DNA binding activity and κB-transcriptional activity. These results indicate that ghrelin enhances migration of glioma cells is mainly regulated by the GHS-R, CaMKII, AMPK, and NF-κB pathway.

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Section: Ghrelin Induces Migration In Glioma Cellssupporting

confidence: 51%

Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-κB signaling pathway in glioma cells

Chen¹,

Huang

Chen

et al. 2011

J. Cell. Biochem.

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“…Increased levels of GDNF in the urine could serve as a basis for the adjunct diagnosis, monitoring, and treatment of interstitial cystitis in patients with bladder cancer (Okragly et al 1999). Recently, we reported that GDNF increases cell migration and metastasis in gliomas, chondrosarcomas, and oral squamous cell carcinomas (Su et al 2009, Lu et al 2010, Chuang et al 2013. Moreover, it has also been reported that the GDNF expression in colon adenocarcinoma cells may play an important role in the pathogenesis of intestinal ganglioneuromatosis (Qiao et al 2009), where an increased expression of GDNF is associated with diffuse ganglioneuromatosis (Furuta et al 2007).…”

Section: Introductionmentioning

confidence: 93%

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

Huang

Chen

Chiu

et al. 2013

Endocrine-Related Cancer

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Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor, has been shown to affect cancer cell metastasis and invasion. However, the molecular mechanisms underlying GDNF-induced colon cancer cell migration remain unclear. GDNF is found to be positively correlated with malignancy in human colon cancer patients. The migratory activities of two human colon cancer cell lines, HCT116 and SW480, were found to be enhanced in the presence of human GDNF. The expression of vascular endothelial growth factor (VEGF) was also increased in response to GDNF stimulation, along with VEGF mRNA expression and transcriptional activity. The enhancement of GDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Our results also showed that the expression of VEGF receptor 1 (VEGFR1) was increased in response to GDNF stimulation, whereas GDNF-induced cancer cell migration was reduced by a VEGFR inhibitor. The GDNF-induced VEGF expression was regulated by the p38 and PI3K/Akt signaling pathways. Treatment with GDNF increased nuclear hypoxia-inducible factor 1 a (HIF1a) accumulation and its transcriptional activity in a time-dependent manner. Moreover, GDNF increased hypoxia responsive element (HRE)-containing VEGF promoter transcriptional activity but not that of the HRE-deletion VEGF promoter construct. Inhibition of HIF1a by a pharmacological inhibitor or dominant-negative mutant reduced the GDNF-induced migratory activity in human colon cancer cells. These results indicate that GDNF enhances the migration of colon cancer cells by increasing VEGF-VEGFR interaction, which is mainly regulated by the p38, PI3K/Akt, and HIF1a signaling pathways.

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“…The different MAPKs can be divided into 3 main subgroups, that is, the extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase/ stress-activated protein kinases (JNK/SAPK), and p38 (9). MAPKs are commonly activated through phosphorylation cascades, and subsequently phosphorylate a number of effectors that contribute to the regulation of diverse cellular events, including differentiation (10,11), proliferation (12,13), survival (14), migration (15), and invasion (16). MAPK kinase kinase kinase isoform 4 (MAP4K4), a germinal centre protein kinase that belongs to the mammalian STE20/MAP4K family, is implicated in the activation of the JNK/SAPK pathway (17,18).…”

Section: Introductionmentioning

confidence: 99%

ShRNA-Targeted MAP4K4 Inhibits Hepatocellular Carcinoma Growth

Liu

Cai

Zhao

et al. 2011

Clinical Cancer Research

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Purpose: Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is overexpressed in many types of cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC).Experimental Design: MAP4K4 expression was examined in 20 fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which 305 (76%) were positive for hepatitis B surface antigens. The clinical significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and the effects of MAP4K4 silencing on cell proliferation in vitro and tumor growth in vivo were evaluated. Quantitative real-time PCR arrays were employed to identify the MAP4K4-regulated signaling pathways.Results: MAP4K4 was aberrantly overexpressed in HCCs relative to adjacent nontumor liver tissues. This overexpression was significantly associated with larger tumor size, increased histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the MAP4K4 expression reduced cell proliferation, blocked cell cycle at S phase, and increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed in vivo, manifested as retarded tumor xenograft growth. Furthermore, multiple tumor progression-related signaling pathways including JNK, NFkB, and toll-like receptors were repressed by MAP4K4 downregulation.Conclusions: MAP4K4 overexpression is an independent predictor of poor prognosis of HCC patients, and inhibition of its expression might be of therapeutic significance.

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Glial cell‐derived neurotrophic factor increases migration of human chondrosarcoma cells via ERK and NF‐κB pathways

Cited by 34 publications

References 34 publications

Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-κB signaling pathway in glioma cells

Ghrelin induces cell migration through GHS-R, CaMKII, AMPK, and NF-κB signaling pathway in glioma cells

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

ShRNA-Targeted MAP4K4 Inhibits Hepatocellular Carcinoma Growth

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