Epidermal Growth Factor Receptor–Related Protein Inhibits Cell Growth and Invasion in Pancreatic Cancer

Wang, Zhiwei; Sengupta, Radha; Banerjee, Sanjeev; Li, Yiwei; Zhang, Yuxiang; Rahman, Khalilur; Aboukameel, Amro; Mohammad, Ramzi M.; Majumdar, Adhip P.N.; Abbruzzese, James L.; Sarkar, Fazlul H.

doi:10.1158/0008-5472.can-06-1019

Cited by 48 publications

(31 citation statements)

References 35 publications

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“…Fifth, hypoxia-driven upregulation of c-Met seems to contribute to the invasive front in PDAC (40). Taken together, these observations suggest that ligation In the present study, we showed that COLO-357 cells, which express very low levels of endogenous Np-1, were not able to exhibit increased invasiveness in the presence of HGF although these cells are capable of responding to EGF (41) and TGF h-1 (22) with increased invasiveness. However, stable overexpression of Np-1 in these cells resulted in a marked increase in invasiveness in response to HGF, and this effect was abolished by siRNA-mediated down-regulation of c-Met.…”

Section: Cancer Researchsupporting

confidence: 51%

Hepatocyte Growth Factor–Mediated Cell Invasion in Pancreatic Cancer Cells Is Dependent on Neuropilin-1

Matsushita

Götze

Korc³

2007

Cancer Research

122

106

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Neuropilin-1 (Np-1), a receptor for semaphorin 3A and vascular endothelial growth factor, is expressed at high levels in pancreatic ductal adenocarcinoma (PDAC). To assess the potential role of Np-1 in PDAC, COLO-357 pancreatic cancer cells, which express relatively low levels of Np-1, were stably transfected with the Np-1 cDNA. Np-1 overexpression was associated with enhanced cell invasiveness in response to hepatocyte growth factor (HGF), and this effect was abolished by small interfering RNA-mediated down-regulation of c-Met. Conversely, in PANC-1 pancreatic cancer cells, which express relatively high levels of Np-1, suppression of endogenous Np-1 completely abolished HGF-mediated cell invasion. To determine which pathways are involved in Np-1-mediated facilitation of c-Met-dependent cell invasiveness, the effects of HGF on signaling were examined next in sham-transfected and Np-1-overexpressing COLO-357 cells. HGF actions on c-Met tyrosine phosphorylation and p38 mitogen-activated protein kinase (MAPK) activation were increased in Np-1-overexpressing COLO-357 cells by comparison with HGF effects in sham-transfected cells. SB203580, an inhibitor of p38 MAPK, suppressed HGF-induced invasion in Np-1-overexpressing cells, whereas U0126, a MAP/extracellular signalregulated kinase kinase inhibitor, was without effect. PP2, a Src inhibitor, and LY294002, a phosphatidylinositol 3-kinase inhibitor, also suppressed HGF-induced invasion in these cells. Immunoprecipitation studies revealed that Np-1 associated with c-Met, but not with epidermal growth factor receptor, family members. Confocal microscopy indicated that this association occurred on the plasma membrane and that HGF promoted the internalization of Np-1-c-Met complex, leading to its perinuclear localization. These findings indicate that Np-1 is required for efficient activation of c-Met-dependent pathways that promote cell invasiveness.

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Section: Cancer Researchsupporting

confidence: 51%

Hepatocyte Growth Factor–Mediated Cell Invasion in Pancreatic Cancer Cells Is Dependent on Neuropilin-1

Matsushita

Götze

Korc³

2007

Cancer Research

122

106

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“…The transfected cells (5 Â 10 3 ) were seeded in a 96-well culture plate and subsequently incubated with MTT reagent (1.0 mg/mL) at 37jC for 2 h, and MTT assay was performed as described earlier (16). The results were plotted as mean F SD of three separate experiments having six determinations per experiment for each experimental condition.…”

Section: Methodsmentioning

confidence: 99%

Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling

et al. 2007

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“…FoxM1 siRNA and siRNA control were obtained from Santa Cruz Biotechnology. The FoxM1 cDNA plasmid was purchased from OriGene Technologies Inc. Human PC cells were transfected with FoxM1 siRNA and cDNA, respectively, using LipofectAMINE 2000 as described earlier (16).…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells

et al. 2007

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The Forkhead Box M1 (FoxM1) transcription factor has been shown to play important roles in regulating the expression of genes involved in cell proliferation, differentiation, and transformation. Overexpression of FoxM1 has been found in a variety of aggressive human carcinomas including pancreatic cancer. However, the precise role and the molecular mechanism of action of FoxM1 in pancreatic cancer remain unclear. To elucidate the cellular and molecular function of FoxM1, we tested the consequences of down-regulation and up-regulation of FoxM1 in pancreatic cancer cells, respectively. Using multiple cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, gene transfection, flow cytometry, real-time reverse transcription-PCR, Western blotting, migration, invasion, and angiogenesis assays, we found that down-regulation of FoxM1 inhibited cell growth, decreased cell migration, and decreased invasion of pancreatic cancer cells. FoxM1 down-regulation also decreased cell population in the S phase. Compared with control, FoxM1 small interfering RNA-transfected cells showed decreased expression of cyclin B, cyclin D1, and Cdk2, whereas p21 and p27 expression was increased. We also found that down-regulation of FoxM1 reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor, resulting in the inhibition of migration, invasion, and angiogenesis. These findings suggest that FoxM1 down-regulation could be a novel approach for the inhibition of pancreatic tumor progression. [Cancer Res 2007;67(17):8293-300]

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Epidermal Growth Factor Receptor–Related Protein Inhibits Cell Growth and Invasion in Pancreatic Cancer

Cited by 48 publications

References 35 publications

Hepatocyte Growth Factor–Mediated Cell Invasion in Pancreatic Cancer Cells Is Dependent on Neuropilin-1

Hepatocyte Growth Factor–Mediated Cell Invasion in Pancreatic Cancer Cells Is Dependent on Neuropilin-1

Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling

Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells

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