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| Status |
Public on Mar 05, 2015 |
| Title |
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis [expression] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1’s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.
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| Overall design |
The microarray data includes two different ages of mouse lung samples.
The microarray for the study on late stage was did on 12-month-old wild type mouse lungs and Ptend/dSmad4d/d mouse lung tumors. This study was used to identify the significantly changed genes between lung tumors and wild type lungs.
The microarray for the study on early stage was did on 7-month-old wild type, Ptend/d and Ptend/dSmad4d/d mouse lungs. This study was used to identify the significantly changed driven genes before the lung tumor initiation and metastasis.
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| Contributor(s) |
Liu J, Cho SN, Akkanti B, Jin N, Mao J, Long W, Chen T, Zhang Y, Tang X, Wistuba II, Creighton CJ, Kheradmand F, DeMayo FJ |
| Citation(s) |
25753424 |
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| Submission date |
Apr 28, 2014 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Jian Liu |
| E-mail(s) |
JianL@intl.zju.edu.cn
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| Organization name |
Zhejiang University
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| Department |
Zhejiang University - University of Edinburgh Institute
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| Lab |
Jian Liu's lab
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| Street address |
718 East Haizhou Rd.
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| City |
Haining |
| State/province |
Zhejiang |
| ZIP/Postal code |
314400 |
| Country |
China |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA245533 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE57133_RAW.tar |
55.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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