VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway

Chang Han Chen, Jin Mei Lai, Teh Ying Chou, Cheng Yu Chen, Li Jen Su, Yuan Chii Lee, Tai Shan Cheng, Yi Ren Hong, Chen Kung Chou, Jacqueline Whang-Peng, Yu Chung Wu, Chi Ying F Huang

Research output: Contribution to journalArticle

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Abstract

Background: Lung adenocarcinoma is the leading cause of cancer-related deaths among both men and women in the world. Despite recent advances in diagnosis and treatment, the mortality rates with an overall 5-year survival of only 15%. This high mortality is probably attributable to early metastasis. Although several well-known markers correlated with poor/metastasis prognosis in lung adenocarcinoma patients by immunohistochemistry was reported, the molecular mechanisms of lung adenocarcinoma development are still not clear. To explore novel molecular markers and their signaling pathways will be crucial for aiding in treatment of lung adenocarcinoma patients. Methodology/Principal Findings: To identify novel lung adenocarcinoma-associated/metastasis genes and to clarify the underlying molecular mechanisms of these targets in lung cancer progression, we created a bioinformatics scheme consisting of integrating three gene expression profile datasets, including pairwise lung adenocarcinoma, secondary metastatic tumors vs. benign tumors, and a series of invasive cell lines. Among the novel targets identified, FLJ10540 was overexpressed in lung cancer tissues and is associated with cell migration and invasion. Furthermore, we employed two coexpression strategies to identify in which pathway FLJ10540 was involved. Lung adenocarcinoma array profiles and tissue microarray IHC staining data showed that FLJ10540 and VEGF-A, as well as FLJ10540 and phospho-AKT exhibit positive correlations, respectively. Stimulation of lung cancer cells with VEGF-A results in an increase in FLJ10540 protein expression and enhances complex formation with PI3K. Treatment with VEGFR2 and PI3K inhibitors affects cell migration and invasion by activating the PI3K/ AKT pathway. Moreover, knockdown of FLJ10540 destabilizes formation of the P110-α/P85-α-(PI3K) complex, further supporting the participation of FLJ10540 in the VEGF-A/PI3K/AKT pathway. Conclusions/Significance: This finding set the stage for further testing of FLJ10540 as a new therapeutic target for treating lung cancer and may contribute to the development of new therapeutic strategies that are able to block the PI3K/AKT pathway in lung cancer cells.

Original languageEnglish
Article numbere5052
JournalPLoS One
Volume4
Issue number4
DOIs
Publication statusPublished - Apr 1 2009

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phosphatidylinositol 3-kinase
lung neoplasms
adenocarcinoma
Phosphatidylinositol 3-Kinases
Lung Neoplasms
Up-Regulation
lungs
vascular endothelial growth factor A
Vascular Endothelial Growth Factor A
metastasis
Cells
cell invasion
Neoplasm Metastasis
Tumors
cell movement
neoplasms
Cell Movement
Tissue
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chen, C. H., Lai, J. M., Chou, T. Y., Chen, C. Y., Su, L. J., Lee, Y. C., ... Huang, C. Y. F. (2009). VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway. PLoS One, 4(4), [e5052]. https://doi.org/10.1371/journal.pone.0005052

VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway. / Chen, Chang Han; Lai, Jin Mei; Chou, Teh Ying; Chen, Cheng Yu; Su, Li Jen; Lee, Yuan Chii; Cheng, Tai Shan; Hong, Yi Ren; Chou, Chen Kung; Whang-Peng, Jacqueline; Wu, Yu Chung; Huang, Chi Ying F.

In: PLoS One, Vol. 4, No. 4, e5052, 01.04.2009.

Research output: Contribution to journalArticle

Chen, CH, Lai, JM, Chou, TY, Chen, CY, Su, LJ, Lee, YC, Cheng, TS, Hong, YR, Chou, CK, Whang-Peng, J, Wu, YC & Huang, CYF 2009, 'VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway', PLoS One, vol. 4, no. 4, e5052. https://doi.org/10.1371/journal.pone.0005052
Chen, Chang Han ; Lai, Jin Mei ; Chou, Teh Ying ; Chen, Cheng Yu ; Su, Li Jen ; Lee, Yuan Chii ; Cheng, Tai Shan ; Hong, Yi Ren ; Chou, Chen Kung ; Whang-Peng, Jacqueline ; Wu, Yu Chung ; Huang, Chi Ying F. / VEGFA upregulates FLJ10540 and modulates migration and invasion of lung cancer via PI3K/AKT pathway. In: PLoS One. 2009 ; Vol. 4, No. 4.
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abstract = "Background: Lung adenocarcinoma is the leading cause of cancer-related deaths among both men and women in the world. Despite recent advances in diagnosis and treatment, the mortality rates with an overall 5-year survival of only 15{\%}. This high mortality is probably attributable to early metastasis. Although several well-known markers correlated with poor/metastasis prognosis in lung adenocarcinoma patients by immunohistochemistry was reported, the molecular mechanisms of lung adenocarcinoma development are still not clear. To explore novel molecular markers and their signaling pathways will be crucial for aiding in treatment of lung adenocarcinoma patients. Methodology/Principal Findings: To identify novel lung adenocarcinoma-associated/metastasis genes and to clarify the underlying molecular mechanisms of these targets in lung cancer progression, we created a bioinformatics scheme consisting of integrating three gene expression profile datasets, including pairwise lung adenocarcinoma, secondary metastatic tumors vs. benign tumors, and a series of invasive cell lines. Among the novel targets identified, FLJ10540 was overexpressed in lung cancer tissues and is associated with cell migration and invasion. Furthermore, we employed two coexpression strategies to identify in which pathway FLJ10540 was involved. Lung adenocarcinoma array profiles and tissue microarray IHC staining data showed that FLJ10540 and VEGF-A, as well as FLJ10540 and phospho-AKT exhibit positive correlations, respectively. Stimulation of lung cancer cells with VEGF-A results in an increase in FLJ10540 protein expression and enhances complex formation with PI3K. Treatment with VEGFR2 and PI3K inhibitors affects cell migration and invasion by activating the PI3K/ AKT pathway. Moreover, knockdown of FLJ10540 destabilizes formation of the P110-α/P85-α-(PI3K) complex, further supporting the participation of FLJ10540 in the VEGF-A/PI3K/AKT pathway. Conclusions/Significance: This finding set the stage for further testing of FLJ10540 as a new therapeutic target for treating lung cancer and may contribute to the development of new therapeutic strategies that are able to block the PI3K/AKT pathway in lung cancer cells.",
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AU - Lai, Jin Mei

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AU - Chen, Cheng Yu

AU - Su, Li Jen

AU - Lee, Yuan Chii

AU - Cheng, Tai Shan

AU - Hong, Yi Ren

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AU - Whang-Peng, Jacqueline

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