Journal
BMC CANCER
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12885-015-1295-9
Keywords
ACTN4; Cytoskeleton organization; Metastasis; Lung cancer; Brain tumor
Categories
Funding
- National Natural Science Foundation of China [81372696]
- China Postdoctoral Science Foundation [2013 M541314]
- Jilin Provincial Science and Technology Department [20090175, 20100733]
- Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry [2009-36]
- Health and Family Planning Commission of Jilin Province [2010Z068]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, Human Resources and Social Security Department of Jilin Province [2012-2014]
- Postdoctoral Science Foundation of Jilin Province
- Human Resources and Social Security Department of Jilin Province
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Background: The aim of this study was to identify critical gene pathways that are associated with lung cancer metastasis to the brain. Methods: The RNA-Seq approach was used to establish the expression profiles of a primary lung cancer, adjacent benign tissue, and metastatic brain tumor from a single patient. The expression profiles of these three types of tissues were compared to define differentially expressed genes, followed by serial-cluster analysis, gene ontology analysis, pathway analysis, and knowledge-driven network analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the expression of essential candidate genes in tissues from ten additional patients. Results: Differential gene expression among these three types of tissues was classified into multiple clusters according to the patterns of their alterations. Further bioinformatic analysis of these expression profile data showed that the network of the signal transduction pathways related to actin cytoskeleton reorganization, cell migration, and adhesion was associated with lung cancer metastasis to the brain. The expression of ACTN4 (actinin, alpha 4), a cytoskeleton protein gene essential for cytoskeleton organization and cell motility, was significantly elevated in the metastatic brain tumor but not in the primary lung cancer tissue. Conclusions: The signaling pathways involved in the regulation of cytoskeleton reorganization, cell motility, and focal adhesion play a role in the process of lung cancer metastasis to the brain. The contribution of ACTN4 to the process of lung cancer metastasis to the brain could be mainly through regulation of actin cytoskeleton reorganization, cell motility, and focal adhesion.
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