Quantitative proteomic profiling of tumor-associated vascular endothelial cells in colorectal cancer

SummeryTo investigate the global proteomic profiles of vascular endothelial cells (VECs) in the tumor microenvironment and antiangiogenic therapy for colorectal cancer (CRC), matched pairs of normal (NVECs) and tumor-associated VECs (TVECs) were purified from CRC tissues by laser capture microdissection and subjected to iTRAQ based quantitative proteomics analysis. Here, 216 differentially expressed proteins (DEPs) were identified and performed bioinformatics analysis. Interestingly, these proteins were implicated in epithelial mesenchymal transition (EMT), ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, angiogenesis and HIF-1 signaling pathway, which may play important roles in CRC angiogenesis. Among these DEPs, Tenascin-C (TNC) was found to upregulated in the TVECs of CRC and be correlate with CRC multistage carcinogenesis and metastasis. Furthermore, the reduction of tumor-derived TNC could attenuate human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation through ITGB3/FAK/Akt signaling pathway. Based on the present work, we provided a large-scale proteomic profiling of VECs in CRC with quantitative information, a certain number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC.Summery statementWe provided large-scale proteomic profiling of vascular endothelial cells in colorectal cancer with quantitative information, a number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC.

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VEGF promotes cardiac stem cells differentiation into vascular endothelial cells via the PI3K/Akt signaling pathway

Artificial Cells Nanomedicine and Biotechnology ◽

10.3109/21691401.2013.837473 ◽

2013 ◽

Vol 42 (6) ◽

pp. 400-405 ◽

Cited By ~ 12

Author(s):

Nuan Xiao ◽

Xiao-Yong Qi ◽

Lu-Ning Tang ◽

Li-Li Tan ◽

Ya-Qing Chen ◽

...

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Signaling Pathway ◽

Vascular Endothelial Cells ◽

Akt Signaling ◽

Cardiac Stem Cells ◽

Vascular Endothelial ◽

Akt Signaling Pathway

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Kaji-Ichigoside F1 and Rosamultin Protect Vascular Endothelial Cells against Hypoxia-Induced Apoptosis via the PI3K/AKT or ERK1/2 Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/6837982 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Chaofeng Shi ◽

Li Zhan ◽

Yuqiang Wu ◽

Zhengchao Li ◽

Jianyu Li ◽

...

Keyword(s):

Endothelial Cells ◽

Signaling Pathway ◽

Vascular Endothelial Cells ◽

Akt Signaling ◽

Western China ◽

Vascular Endothelial ◽

Akt Signaling Pathway ◽

Pharmacodynamic Analysis ◽

Regulatory Effects ◽

Induced Apoptosis

As a pair of differential isomers, Kaji-ichigoside F1 and Rosamultin are both pentacyclic triterpenoids isolated from the subterranean root of Potentilla anserina L., a plant used in folk medicine in western China as antihypoxia and anti-inflammatory treatments. We demonstrated that Kaji-ichigoside F1 and Rosamultin effectively prevented hypoxia-induced apoptosis in vascular endothelial cells. We established a hypoxia model, using EA.hy926 cells, to further explore the mechanisms. Hypoxia promoted the phosphorylation of AKT, ERK1/2, and NF-κB. In hypoxic cells treated with Kaji-ichigoside F1, p-ERK1/2 and p-NF-κB levels were increased, while the level of p-AKT was decreased. Treatment with Rosamultin promoted phosphorylation of ERK1/2, NF-κB, and AKT in hypoxic cells. Following the addition of LY294002, the levels of p-AKT, p-ERK1/2, and p-NF-κB decreased significantly. Addition of PD98059 resulted in reduced levels of p-ERK1/2 and p-NF-κB, while p-AKT levels were increased. Pharmacodynamic analysis demonstrated that both LY294002 and PD98059 significantly inhibited the positive effects of Kaji-ichigoside F1 on cell viability during hypoxia, consistent with the results of hematoxylin-eosin (H&E) staining, DAPI staining, and flow cytometry. The antihypoxia effects of Rosamultin were remarkably inhibited by LY294002 but promoted by PD98059. In Kaji-ichigoside F1- and Rosamultin-treated cells, Bcl2 expression was significantly upregulated, while expression of Bax and cytochrome C and levels of cleaved caspase-9 and cleaved caspase-3 were reduced. Corresponding to pharmacodynamic analysis, LY294002 inhibited the regulatory effects of Kaji-ichigoside F1 and Rosamultin on the above molecules, while PD98059 inhibited the regulatory effects of Kaji-ichigoside F1 but enhanced the regulatory effects of Rosamultin. In conclusion, Kaji-ichigoside F1 protected vascular endothelial cells against hypoxia-induced apoptosis by activating the ERK1/2 signaling pathway, which positively regulated the NF-κB signaling pathway and negatively regulated the PI3K/AKT signaling pathway. Rosamultin protected vascular endothelial cells against hypoxia-induced apoptosis by activating the PI3K/AKT signaling pathway and positively regulating ERK1/2 and NF-κB signaling pathways.

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Quantitative proteomic profiling of tumor-associated vascular endothelial cells in colorectal cancer

Biology Open ◽

10.1242/bio.042838 ◽

2019 ◽

Vol 8 (5) ◽

pp. bio042838 ◽

Cited By ~ 7

Author(s):

Guoqiang Wang ◽

Qiongzhi Yang ◽

Maoyu Li ◽

Ye Zhang ◽

Yuxiang Cai ◽

...

Keyword(s):

Colorectal Cancer ◽

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Proteomic Profiling

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PI3K/Akt/uncoupling protein 2 signaling pathway may be involved in cell senescence and apoptosis induced by angiotensin II in human vascular endothelial cells

Molecular Biology Reports ◽

10.1007/s11033-014-3580-0 ◽

2014 ◽

Vol 41 (10) ◽

pp. 6931-6937 ◽

Cited By ~ 13

Author(s):

Ping Li ◽

Xin Guo ◽

Pingping Lei ◽

Shoujun Shi ◽

Shike Luo ◽

...

Keyword(s):

Endothelial Cells ◽

Angiotensin Ii ◽

Signaling Pathway ◽

Vascular Endothelial Cells ◽

Uncoupling Protein ◽

Cell Senescence ◽

Uncoupling Protein 2 ◽

Vascular Endothelial

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Knockdown of Nrf2 inhibits angiogenesis by downregulating VEGF expression through PI3K/Akt signaling pathway in cerebral microvascular endothelial cells under hypoxic conditions

Biochemistry and Cell Biology ◽

10.1139/bcb-2017-0291 ◽

2018 ◽

Vol 96 (4) ◽

pp. 475-482 ◽

Cited By ~ 17

Author(s):

Yujing Huang ◽

Ying Mao ◽

Huiying Li ◽

Guangxun Shen ◽

Guangxian Nan

Keyword(s):

Vascular Endothelial Growth Factor ◽

Ischemic Stroke ◽

Growth Factor ◽

Signaling Pathway ◽

Akt Signaling ◽

Tube Formation ◽

Vascular Endothelial ◽

Akt Signaling Pathway ◽

Microvascular Endothelial ◽

Endothelial Growth Factor

Ischemic stroke is a major cerebrovascular disease resulting from a transient or permanent local reduction of cerebral blood flow. Angiogenesis plays an important role in cerebral microvascular repair after ischemic stroke. This study aimed at investigating the effect of NF-E2-related factor 2 (Nrf2) on the angiogenesis of mouse cerebral microvascular endothelial bEnd.3 cells in a hypoxic environment. We found that Nrf2 expression was temporarily increased in hypoxia-induced bEnd.3 cells. Knockdown of Nrf2 inhibited the proliferation, migration, as well as tube formation in hypoxia-induced bEnd.3 cells. Meanwhile, vascular endothelial growth factor and PI3K/Akt signaling pathways were identified to be regulated by Nrf2 in hypoxia-induced bEnd.3 cells. It was found that silencing of Nrf2 downregulated the expression levels of NAD(P)H:quinine oxidoreductase-1, vascular endothelial growth factor, p-Akt, and heme oxygenase-1 in hypoxia-induced bEnd.3 cells. Data suggested that hypoxia induced the transient increase of Nrf2, which plays a key role in the angiogenesis of cerebral microangiogenesis, and that Nrf2 regulates the proliferation, migration, as well as tube formation likely through PI3K/Akt signaling pathway in hypoxia-induced bEnd.3 cells. Our study provides proof of concept for the modulation of Nrf2, so as to tilt the balance toward angiogenesis, representing a therapeutic strategy for hypoxia or ischemia disorders such as stroke.

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YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis Through Activating Yap Signaling in Vascular Endothelial Cells

10.21203/rs.3.rs-27591/v1 ◽

2020 ◽

Author(s):

Yu Yan ◽

Qiang Song ◽

Li Yao ◽

Liang Zhao ◽

Hui Cai

Keyword(s):

Breast Cancer ◽

Endothelial Cells ◽

Cancer Cells ◽

Signaling Pathway ◽

Tumor Angiogenesis ◽

Breast Cancer Cells ◽

Vascular Endothelial Cells ◽

Tissue Growth ◽

Vascular Endothelial ◽

Potential Marker

Abstract Background:The YAP signaling pathway is altered and implicated as oncogenic in human mammary cancers.However, roles of YAP signaling that regulate the breast tumor angiogenesis have remained elusive. Tumor angiogenesis is coordinated by the activation of both cancer cells and vascular endothelial cells. Whether the YAP signalingpathway can regulate the intercellular interaction between cancer cells and endothelial cellsis essentially unknown.Results: We showed here that conditioned media from YAP overexpressed breast cancer cells (CM-YAP+) could promote angiogenesis, accompanied byincreased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). Down regulation of YAP in HUVECs reversed CM-YAP+ induced angiogenesis.CM-YAP+ time-dependently activated YAP inHUVECs by dephosphorylating YAP and increasing nuclear translocation.We also identified that both G13-RhoA and PI3K/Akt signaling pathway were necessary for CM-YAP+ induced activation of YAP.Besides, connective tissue growth factor (CTGF) and angiopoietin-2 (ANG-2)actedas down-stream of YAP in HUVECs to promote angiogenesis.In addition, subcutaneous tumors nude mice model demonstrated that tumors overexpressed YAP revealed moreneovascularization in vivo.Conclusions: YAP-YAP interaction between breastcancer cells and endothelial cellscould promote tumor angiogenesis, supporting that YAP is a potential marker and target fordeveloping novel therapeutic strategies against breast cancer.

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