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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 13, 2012 |
Title |
Claudin 1 mediates TNFα-induced gene expression and cell migration in human lung carcinoma cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Epithelial-mesenchymal transition (EMT) is an important mechanism in carcinogenesis. To determine the mechanisms that are involved in the regulation of EMT is crucial to develop new biomarkers and therapeutic targets towards cancers. In this study, when TGFß1 and TNFa were used to induce EMT in human lung carcinoma A549 cells, we were surprised to find an increase in an epithelial cell tight junction marker, Claudin 1. We further identified that it was the TNFa and not the TGFß1 that induced the fibroblast-like morphology changes. TNFa also caused the increase in Claudin-1 gene expression and protein levels in Triton X-100 soluble cytoplasm fraction. Down-regulation of Claudin-1, using small interfering RNA (siRNA), inhibited 75% of TNFa-induced gene expression changes. Claudin-1 siRNA effectively blocked TNFa-induced molecular functional networks related to inflammation and cell movement. Wound-healing assay showed that Claudin-1 siRNA was able to significantly reduce TNF-enhanced cell migration. Furthermore, over expression of Claudin 1 with a Claudin 1-pcDNA3.1/V5-His vector enhanced cell migration. In conclusion, these observations indicate that Claudin 1 acts as a critical signal mediator in TNFa-induced gene expression and cell migration in human lung cancer cells. Further analyses of these cellular processes may be helpful in developing novel therapeutic strategies.
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Overall design |
4 groups (with or without TNFα, control or Claudin 1 siRNA) of human lung adenocarcinoma A549 cells with 3 replicates per group.
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Contributor(s) |
Shiozaki A, Bai X, Fung S, Keshavjee S, Liu M |
Citation(s) |
22675434 |
Submission date |
Sep 20, 2011 |
Last update date |
Jul 26, 2018 |
Contact name |
Mingyao Liu |
E-mail(s) |
mingyao.liu@utoronto.ca
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Organization name |
University of Toronto
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Department |
Surgery
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Lab |
Latner Research Laboratories
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Street address |
101 College Street
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City |
Toronto |
State/province |
Ontario |
ZIP/Postal code |
M5G 1L7 |
Country |
Canada |
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Platforms (1) |
GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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Samples (12)
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GSM799189 |
A549, +TNFα, control siRNA, rep1 |
GSM799190 |
A549, +TNFα, control siRNA, rep2 |
GSM799191 |
A549, +TNFα, control siRNA, rep3 |
GSM799192 |
A549, -TNFα, Claudin 1 siRNA, rep1 |
GSM799193 |
A549, -TNFα, Claudin 1 siRNA, rep2 |
GSM799194 |
A549, -TNFα, Claudin 1 siRNA, rep3 |
GSM799195 |
A549, +TNFα, Claudin 1 siRNA, rep1 |
GSM799196 |
A549, +TNFα, Claudin 1 siRNA, rep2 |
GSM799197 |
A549, +TNFα, Claudin 1 siRNA, rep3 |
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Relations |
BioProject |
PRJNA147353 |
Supplementary file |
Size |
Download |
File type/resource |
GSE32254_RAW.tar |
49.9 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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