Genomics,Multiomics

Dataset Information

3

Identification of novel tissue-specific transcription arising from E-cadherin/CDH1 intron2: a novel protein isoform increases gastric cancer cell invasion and angiogenesis.


ABSTRACT: E-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach. Results: In this sense we have searched for additional CDH1 transcripts arising from intron 2. From the four found, one (CDH1a) was demonstrated to be tissue specific and to be translated in vivo. When overexpressed in an E-cadherin negative context CDH1a replaced the canonic protein functions Conclusions: We have demonstrated, for the first time, transcripts arising from CDH1 intron 2. One of these, CDH1a, was found to modulate E-cadherin function representing a novel mechanism underlying invasion and angiogenesis in epithelial cancers and opening the way for novel therapeutic approaches. Total RNA obtained from human gastric tubular adenocarcinoma Mkn28 cell line. Three independent replicas of each conditions(i.e pLenti transduced cell lines overexpressing CDH1a , pLenti with empty vector and pLenti transduced cell lines overexpressing wild type CDH1) has been employed.

OTHER RELATED OMICS DATASETS IN: PRJNA147811

ORGANISM(S): Homo sapiens  

SUBMITTER: Hugo H Pinheiro   Danilo D Licastro  Danilo Licastro 

PROVIDER: E-GEOD-32540 | ArrayExpress | 2012-08-01

SECONDARY ACCESSION(S): GSE32540PRJNA147811

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-32540.README.txt Txt
E-GEOD-32540.eSet.r Other
E-GEOD-32540.idf.txt Idf
E-GEOD-32540.processed.1.zip Processed
E-GEOD-32540.raw.1.zip Raw
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Publications

Transcription initiation arising from E-cadherin/CDH1 intron2: a novel protein isoform that increases gastric cancer cell invasion and angiogenesis.

Pinheiro Hugo H   Carvalho Joana J   Oliveira Patrícia P   Ferreira Daniel D   Pinto Marta Teixeira MT   Osório Hugo H   Licastro Danilo D   Bordeira-Carriço Renata R   Jordan Peter P   Lazarevic Dejan D   Sanges Remo R   Stupka Elia E   Huntsman David D   Seruca Raquel R   Oliveira Carla C  

Human molecular genetics 20120629 19


Disruption of E-cadherin (CDH1 gene) expression, subcellular localization or function arises during initiation and progression of almost 90% of all epithelial carcinomas. Nevertheless, the mechanisms through which this occurs are largely unknown. Previous studies showed the importance of CDH1 intron 2 sequences for proper gene and protein expression, supporting these as E-cadherin cis-modulators. Through RACE and RT-PCR, we searched for transcription events arising from CDH1 intron 2 and discove  ...[more]

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