Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

Chen Yun Yeh, Shin Mei Shin, Hsuan Heng Yeh, Tsung Jung Wu, Jyh Wei Shin, Tsuey Yu Chang, Giri Raghavaraju, Chung Ta Lee, Jung Hsien Chiang, Vincent S. Tseng, Yuan Chii G Lee, Cheng Huang Shen, Nan Haw Chow, Hsiao Sheng Liu

研究成果: 雜誌貢獻文章

43 引文 (Scopus)

摘要

Background: A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.Methods: Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.Results: A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p <0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p <0.01).Conclusions: In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.
原文英語
文章編號139
期刊BMC Cancer
11
DOIs
出版狀態已發佈 - 四月 16 2011

指紋

Platelet-Derived Growth Factor alpha Receptor
Receptor Protein-Tyrosine Kinases
Urinary Bladder Neoplasms
Transcriptional Activation
Small Interfering RNA
Receptor Cross-Talk
Survival
Extracellular Signal-Regulated MAP Kinases
Microarray Analysis
RNA Interference
Mitogen-Activated Protein Kinases
Western Blotting
Cell Line
Genes
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

引用此文

Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer. / Yeh, Chen Yun; Shin, Shin Mei; Yeh, Hsuan Heng; Wu, Tsung Jung; Shin, Jyh Wei; Chang, Tsuey Yu; Raghavaraju, Giri; Lee, Chung Ta; Chiang, Jung Hsien; Tseng, Vincent S.; Lee, Yuan Chii G; Shen, Cheng Huang; Chow, Nan Haw; Liu, Hsiao Sheng.

於: BMC Cancer, 卷 11, 139, 16.04.2011.

研究成果: 雜誌貢獻文章

Yeh, CY, Shin, SM, Yeh, HH, Wu, TJ, Shin, JW, Chang, TY, Raghavaraju, G, Lee, CT, Chiang, JH, Tseng, VS, Lee, YCG, Shen, CH, Chow, NH & Liu, HS 2011, 'Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer', BMC Cancer, 卷 11, 139. https://doi.org/10.1186/1471-2407-11-139
Yeh, Chen Yun ; Shin, Shin Mei ; Yeh, Hsuan Heng ; Wu, Tsung Jung ; Shin, Jyh Wei ; Chang, Tsuey Yu ; Raghavaraju, Giri ; Lee, Chung Ta ; Chiang, Jung Hsien ; Tseng, Vincent S. ; Lee, Yuan Chii G ; Shen, Cheng Huang ; Chow, Nan Haw ; Liu, Hsiao Sheng. / Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer. 於: BMC Cancer. 2011 ; 卷 11.
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title = "Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer",
abstract = "Background: A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.Methods: Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.Results: A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p <0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p <0.01).Conclusions: In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.",
keywords = "AxlPDGFR-αC-Met, Bladder cancer",
author = "Yeh, {Chen Yun} and Shin, {Shin Mei} and Yeh, {Hsuan Heng} and Wu, {Tsung Jung} and Shin, {Jyh Wei} and Chang, {Tsuey Yu} and Giri Raghavaraju and Lee, {Chung Ta} and Chiang, {Jung Hsien} and Tseng, {Vincent S.} and Lee, {Yuan Chii G} and Shen, {Cheng Huang} and Chow, {Nan Haw} and Liu, {Hsiao Sheng}",
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T1 - Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

AU - Yeh, Chen Yun

AU - Shin, Shin Mei

AU - Yeh, Hsuan Heng

AU - Wu, Tsung Jung

AU - Shin, Jyh Wei

AU - Chang, Tsuey Yu

AU - Raghavaraju, Giri

AU - Lee, Chung Ta

AU - Chiang, Jung Hsien

AU - Tseng, Vincent S.

AU - Lee, Yuan Chii G

AU - Shen, Cheng Huang

AU - Chow, Nan Haw

AU - Liu, Hsiao Sheng

PY - 2011/4/16

Y1 - 2011/4/16

N2 - Background: A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.Methods: Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.Results: A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p <0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p <0.01).Conclusions: In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.

AB - Background: A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers.Methods: Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients.Results: A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p <0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p <0.01).Conclusions: In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.

KW - AxlPDGFR-αC-Met

KW - Bladder cancer

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