Urokinase plasminogen activator receptor is upregulated by Helicobacter pylori in human gastric cancer AGS cells via ERK, JNK, and AP-1

Kim, Mi H.; Yoo, Hyung Sik; Chang, Hee J.; Hong, Min Hee; Kim, Ho D.; Chung, Ik Joo; Shin, Boo Ahn; Cho, Myung J.; Ahn, Bong Whan; Jung, Young Do

doi:10.1016/j.bbrc.2005.06.002

Cited by 19 publications

(28 citation statements)

References 24 publications

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“…The total RNA extraction and Northern blot hybridization were performed as previously described (18). Each cDNA probe was radiolabeled with [·-…”

Section: Matrigel Invasion Assaymentioning

confidence: 99%

“…The transcriptional regulation of uPAR was examined using the transient transfection with a uPAR promoter-luciferase reporter construct (pGL3-uPAR) (18). The plasmid pGL3/uPARpromoter was kindly provided by Dr Y. Wang (Australian National University, Canberra, Australia).…”

Section: Measurement Of Upar Promoter Activitymentioning

confidence: 99%

“…1B). It was suggested that uPAR is essential for the invasive phenotype of cancer cells (18). The role of H. pylori-induced uPAR in the AGS cell invasion was examined by incubating the cells with specific antibodies to uPAR in a modified Boyden invasion chamber.…”

Section: Effect Of H Pylori On the Induction Of Upar And Cellmentioning

confidence: 99%

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Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-κB signaling in human gastric carcinoma cells

Yoo²,

Jang³

et al. 2007

Int J Mol Med

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Abstract. The gastric pathogen, helicobacter pylori (H. pylori), has been associated with the progression of gastric cancer. It was previously reported that H. pylori induced urokinase plasminogen activator receptor (uPAR) expression and stimulated cell invasiveness in human gastric cancer AGS cells. However, the precise mechanisms for how H. pylori upregulates uPAR are unclear. This study investigated the underlying signal pathways in H. pylori-induced uPAR in human gastric cancer AGS cells. The intracellular H 2 O 2 content, as determined using H 2 O 2 -sensitive probe 2',7'-dichlorodihydrofluorescein, increased after the H. pylori treatment. N-acetyl cysteine (NAC), an antioxidant, prevented the H. pylori-induced production of H 2 O 2 and uPAR expression. In addition, exogenous H 2 O 2 was found to increase uPAR mRNA expression and its promoter activity. Sitedirected mutagenesis of the potential NF-κB element in the uPAR promoter showed that the redox-sensitive transcription factor NF-κB was essential for H. pylori-induced uPAR expression. The expression of vectors encoding a mutatedtype NF-κB-inducing kinase and I-κB, and a specific inhibitor of NF-κB (BAY11-7082) decreased the H. pyloriinduced uPAR promoter activity. Chromatin immunoprecipitation and the electrophoretic mobility shift assay confirmed that H. pylori increased the DNA binding activity of NF-κB. With the aid of NAC and H 2 O 2 , it was determined that reactive oxygen species (ROS) is an upstream signaling molecule for activating the NF-κB induced by H. pylori. The enhanced AGS cell invasiveness by H. pylori was partially abrogated by an NAC and BAY11-7082 treatment. These results suggest that the ROS and NF-κB signaling pathway is important in H. pylori-induced uPAR expression and the increased cell invasiveness of human gastric cancer AGS cells.

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“…The total RNA extraction and Northern blot hybridization were performed as previously described (18). Each cDNA probe was radiolabeled with [·-…”

Section: Matrigel Invasion Assaymentioning

confidence: 99%

Section: Measurement Of Upar Promoter Activitymentioning

confidence: 99%

See 1 more Smart Citation

Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-κB signaling in human gastric carcinoma cells

Yoo²,

Jang³

et al. 2007

Int J Mol Med

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“…pylori has been related to induction of uPAR. Several in vitro studies have found that the expression of uPAR is upregulated in cancer and gastric epithelial cell lines when co-cultured with H. pylori (Guillemin, Salama, Tompkins, & Falkow, 2002;Sepulveda et al, 2002;El-Etr, Mueller, Tompkins, Falkow, & Merrell, 2004;Iwamoto et al, 2005;Kim et al, 2005;Kim et al, 2007;Iwamoto, Mizokami, Takahashi, Matsuoka, & Matsuzaki, 2008). This phenomenon has also been documented in vivo, specifically in non-neoplastic tissue (adjacent to the tumor growth) obtained from GC patients (Alpízar-Alpízar et al, 2010), as well as in gastric biopsies from patients that have no cancer but are infected with the bacterium (Kenny et al, 2008).…”

Section: Plasminogen Activation System and Helicobacter Pylorimentioning

confidence: 82%

“…AP-1, another transcription factor commonly associated to the induction of uPAR (Lengyel et al, 1996b;Baek et al, 2008), is activated as a result of H. pylori infection (Naumann et al, 2017). This means that AP-1 may also be a factor implicated in the induction of uPAR in response to this infection (Kim et al, 2005). A commonality of the induction of uPAR mediated by NF-κB or AP-1 is that ERK signaling pathway can lead to activation of both transcriptional regulators (Lengyel et al, 1996a;Baek et al, 2008).…”

Section: Plasminogen Activation System and Helicobacter Pylorimentioning

confidence: 99%

La importancia del sistema activador de plasminógeno en la patogénesis y progresión del cáncer gástrico

Alpízar‐Alpízar

Malespín-Bendaña

Une

et al. 2017

RBT

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Gastric cancer is ranked as the third death-causing cancer and one of the most incident malignancies worldwide. Although Helicobacter pylori is the most well-established risk factor for the development of this neoplasm, most of the infected individuals do not develop gastric cancer. Two of the main challenges faced by the world's scientific community in the combat against gastric cancer are the unraveling of its pathogenesis and the identification of novel ways to bring down the mortality. Malignant cell invasion of the non-neoplastic adjacent tissue and metastasis are pivotal events during cancer development and progression. Both processes are facilitated by proteases capable of degrading components of the extracellular matrix, some of which have been associated to clinic-pathological aspects of the disease. Recent studies have suggested the possible connection between H. pylori and the expression of some of these proteases in gastric mucosa. This review summarizes the current knowledge about epidemiological, clinical and biological aspects of gastric cancer; it also discusses the main findings about the involvement of the plasminogen activation system in the development and progression of this disease, as well as its potential repercussions in the clinical setting. Rev. Biol. Trop. 66(1): 28-47. Epub 2018 March 01.

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Urokinase plasminogen activator receptor is expressed in invasive cells in gastric carcinomas from high‐ and low‐risk countries

Alpízar‐Alpízar

Nielsen

Sierra

et al. 2009

Intl Journal of Cancer

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Gastric cancer is the second cancer causing death worldwide. Both incidence and mortality rates vary according to geographical regions. The receptor for urokinase plasminogen activator (uPAR) is involved in extracellular matrix degradation by mediating cell surface associated plasminogen activation, and its presence on gastric cancer cells is linked to micrometastasis and poor prognosis. Immunohistochemical analyses of a set of 44 gastric cancer lesions from Costa Rica showed expression of uPAR in cancer cells in both intestinal subtype (14 of 27) and diffuse subtype (10 of 17). We compared the expression pattern of uPAR in gastric cancers from a high-risk country (Costa Rica) with a low-risk country (Norway). We found uPAR on gastric cancer cells in 24 of 44 cases (54%) from Costa Rica and in 13 of 23 cases (56%) from Norway. uPAR was seen in macrophages and neutrophils in all cases. We also examined the nonneoplastic mucosa and found that uPAR was more frequently seen in epithelial cells located at the luminal edge of the crypts in cases with Helicobacter pylori infection than in similar epithelial cells in noninfected mucosa (p 5 0.033; v 2 5 4.54). In conclusion, the expression of uPAR in cancer cells in more than half of the gastric cancer cases suggests that their uPAR-positivity do not contribute to explain the different mortality rates between the 2 countries, however, the actual prevalence of uPAR-positive cancer cells in the gastric cancers may still provide prognostic information.Gastric cancer is the second most common cancer causing death worldwide after lung cancer and is a final result of the stepwise process initiated by environmental factors including diet and Helicobacter pylori infection. [1][2][3] In particular, H. pylori infection is one of the most recognized risk factors for this malignancy. 4-6 Both the incidence and mortality rates of gastric cancer present substantial variations according to geographical regions (between and within countries). 1 The factors explaining these variations remain unknown so far given the complexity and multifactorial nature of the disease. Costa Rica is one of the countries with highest incidence and mortality rates for gastric cancer worldwide. In contrast, most of western European countries present low incidence and low mortality rates for this malignancy. 1,7 Among the key events for cancer development and progression are neoplastic cell invasion into the adjacent normal tissue and eventually metastasis. Invasion and metastasis are facilitated by a number of proteinases capable of degrading the extracellular matrix (ECM). 8,9 Plasmin can degrade major ECM proteins like fibrin, fibronectin and laminin and in

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Urokinase plasminogen activator receptor is upregulated by Helicobacter pylori in human gastric cancer AGS cells via ERK, JNK, and AP-1

Cited by 19 publications

References 24 publications

Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-κB signaling in human gastric carcinoma cells

Helicobacter pylori stimulates urokinase plasminogen activator receptor expression and cell invasiveness through reactive oxygen species and NF-κB signaling in human gastric carcinoma cells

La importancia del sistema activador de plasminógeno en la patogénesis y progresión del cáncer gástrico

Urokinase plasminogen activator receptor is expressed in invasive cells in gastric carcinomas from high‐ and low‐risk countries

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