Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches

Scartozzi, Mario; Galizia, Eva; Freddari, Federica; Berardi, Rossana; Cellerino, R; Cascinu, Stefano

doi:10.1016/j.ctrv.2004.01.001

Cited by 61 publications

(49 citation statements)

References 43 publications

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“…Several means of silencing E-cadherin gene expression in gastric carcinoma have been observed, including methylation of the E-cadherin promoter, E-cadherin gene truncation mutations and loss of heterozygosity of the E-cadherin locus (Rosivatz et al, 2002;Brooks-Wilson et al, 2004;Scartozzi et al, 2004;Yang et al, 2004). However, these mechanisms account for only a portion of the E-cadherin-negative gastric carcinomas.…”

Section: Disruption Of E-cadherin Function By Tgf-b Adaptor Elfmentioning

confidence: 99%

Critical interactions between TGF-β signaling/ELF, and E-cadherin/β-catenin mediated tumor suppression

Katuri

Tang

et al. 2006

Oncogene

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Inactivation of the transforming growth factor-b (TGF-b) pathway occurs often in malignancies of the gastrointestinal (GI) system. However, only a fraction of sporadic GI tumors exhibit inactivating mutations in early stages of cancer formation, suggesting that other mechanisms play a critical role in the inactivation of this pathway. Here, we show a wide range of GI tumors, including those of the stomach, liver and colon in elf þ /À and elf þ /À /Smad4 þ /À mutant mice. We found that embryonic liver fodrin (ELF), a b-Spectrin originally identified in endodermal stem/ progenitor cells committed to foregut lineage, possesses potent antioncogenic activity and is frequently inactivated in GI cancers. Specifically, E-cadherin accumulation at cell-cell contacts and E-cadherin-b-catenin-dependent epithelial cell-cell adhesion is disrupted in elf þ /À / Smad4 þ /À mutant gastric epithelial cells, and could be rescued by ectopic expression of full-length elf, but not Smad3 or Smad4. Subcellular fractionation revealed that E-cadherin is expressed mainly at the cell membrane after TGF-b stimulation. In contrast, elf þ /À /Smad4 þ /À mutant tissues showed abnormal distribution of E-cadherin that could be rescued by overexpression of ELF but not Smad3 or Smad4. Our results identify a group of common lethal malignancies in which inactivation of TGF-b signaling, which is essential for tumor suppression, is disrupted by inactivation of the ELF adaptor protein.

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Section: Disruption Of E-cadherin Function By Tgf-b Adaptor Elfmentioning

confidence: 99%

Critical interactions between TGF-β signaling/ELF, and E-cadherin/β-catenin mediated tumor suppression

Katuri

Tang

et al. 2006

Oncogene

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“…However, loss of E-cadherin expression was much more frequent in carcinomas that metastasize to distant organs than in those which do not [22]. On the other hand, Scartozzi et al [23] observed "abnormal" E-cadherin expression more frequently in diffuse-type gastric cancer than in intestinal type according to Lauren's classification. Karayiannakis et al [24] found a significant correlation of "abnormal" E-cadherin expression with tumor differentiation grade, location and lymph node involvement.…”

Section: Discussionmentioning

confidence: 96%

The expression of E-cadherin-catenin complex in patients with advanced gastric cancer: role in formation of metastasis.

Czyżewska

Guzińska‐Ustymowicz²,

Ustymowicz³

et al. 2010

Folia Histochem Cytobiol.

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“…Genomic amplification is one of the most common types of genetic abnormalities encountered in gastric cancer and frequently leads to the overexpression of genes that may affect cellular behavior. Therefore, the identification of the genes residing at the genomic amplification regions may help researchers elucidate the details of the tumorigenic processes in gastric cancer and identify diagnostic and/or prognostic markers, which may also serve as novel target molecules for the treatment of this disease (4,5).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma

Dinccelik-Aslan

Gümüş-Akay

Elhan

et al. 2015

Molecular and Clinical Oncology

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Abstract. Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer-related mortality. Previous studies revealed several genetic alterations specific to gastric cancer. In this study, we aimed to investigate the diagnostic and prognostic significance of the expression levels of the glypican 5 and glypican 6 genes (GPC5 and GPC6, respectively) in gastric cancer. For this purpose, GPC5 and GPC6 expression was quantitatively determined by quantitative polymerase chain reaction method in normal gastric mucosa and intestinal type gastric adenocarcinoma samples from 35 patients. The expression levels of GPC5 and GPC6 were compared between normal and tumor tissues. Additionally, the association of the expression levels in tumor tissues with several clinicopathological parameters was evaluated. Although GPC5 was not expressed in any of the samples, the expression of GPC6, which was detected in both groups, was found to be significantly higher in tumor tissues compared to that in normal samples (P=0.039). However, there was no statistically significant association between GPC6 expression and any of the clinicopathological parameters investigated (P>0.05). Our findings suggested that an increase in GPC6 expression levels may be implicated in gastric cancer development, but not in cancer progression.

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Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches

Cited by 61 publications

References 43 publications

Critical interactions between TGF-β signaling/ELF, and E-cadherin/β-catenin mediated tumor suppression

Critical interactions between TGF-β signaling/ELF, and E-cadherin/β-catenin mediated tumor suppression

The expression of E-cadherin-catenin complex in patients with advanced gastric cancer: role in formation of metastasis.

Diagnostic and prognostic significance of glypican 5 and glypican 6 gene expression levels in gastric adenocarcinoma

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