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Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

by Tang, H , Cao, D , Xu, Z-F , Wu, K , Ding, X-Y , Ding, J , Guo, L-N , Yan, H-X , Gao, C-K , Wen, W , Li, Z , Feng, G-S , Liu, C , Chen, C , Wang, S , Wang, H-Y

in Angiogenesis / Apoptosis / Cancer / Carcinogenesis / Cell Biology / Cell proliferation / Cellular biology / Endothelial cells / Endothelium / Health aspects / Human Genetics / Internal Medicine / Ligands / Lung cancer / Medicine / Medicine & Public Health / Non-small cell lung carcinoma / Notch protein / Notch1 protein / Oncology / Physiological aspects / Prevention / PTEN protein / RNA / RNA-mediated interference / short-communication / Signal transduction / Small cell lung carcinoma / Tumor cells / Tumors / Xenografts

2012

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Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

by Tang, H , Cao, D , Xu, Z-F , Wu, K , Ding, X-Y , Ding, J , Guo, L-N , Yan, H-X , Gao, C-K , Wen, W , Li, Z , Feng, G-S , Liu, C , Chen, C , Wang, S , Wang, H-Y

2012

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Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

by Tang, H , Cao, D , Xu, Z-F , Wu, K , Ding, X-Y , Ding, J , Guo, L-N , Yan, H-X , Gao, C-K , Wen, W , Li, Z , Feng, G-S , Liu, C , Chen, C , Wang, S , Wang, H-Y

2012

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Journal Article

Cross-talk between endothelial cells and tumor via delta-like ligand4/Notch/PTEN signaling inhibits lung cancer growth

Tang, H,

Cao, D,

Xu, Z-F,

Wu, K,

Ding, X-Y,

Ding, J,

Guo, L-N,

Yan, H-X,

Gao, C-K,

Wen, W,

Li, Z,

Feng, G-S,

Liu, C,

Chen, C,

Wang, S,

Wang, H-Y

2012

Overview

Lung cancer is a leading cause of cancer death in many countries. Notch signaling has been demonstrated to frequently participate in the process of lung carcinogenesis. Delta-like ligand 4 (Dll4) is a vascular-specific ligand of Notch, and has a critical role in the angiogenesis of numerous cancers. However, the role of Dll4 in the cross-talk between endothelial cells (ECs) and tumor cells remains obscure. Herein, our study revealed that Dll4-expressing ECs (EC-Dll4) significantly suppressed the proliferation of neighboring non-small cell lung cancer (NSCLC) cells and attenuated the growth of NSCLC xenograft in nude mice. On the contrary, silencing endothelial Dll4 by its specific interference RNA reversed these effects of Dll4 on NSCLC cell proliferation and tumor formation. Furthermore, activation of Notch1, but not Notch2 or Notch3, was enhanced in NSCLC cells cultured with EC-Dll4, as well as in xenografts induced by a mixture of NSCLC cells and EC-Dll4. Interference of Notch1 significantly attenuated Dll4-mediated suppression of NSCLC cell proliferations, indicating that Dll4/Notch1 signaling negatively modulates the NSCLC growth. Moreover, PTEN expression in NSCLC cells was increased by EC-Dll4 or rhDll4 (recombinant human-Dll4 protein), and the induction was impaired by Notch1 interference suggesting that Dll4 could upregulate PTEN expression by Notch1. Taken together, we conclude that the cross-talk between ECs and NSCLC cells by Dll4/Notch1/PTEN signaling pathway inhibits the growth of NSCLC.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

/ Cancer