Gln-362 of Angiopoietin-2 Mediates Migration of Tumor and Endothelial Cells through Association with α5β1 Integrin

Lee, Hyo Seon; Oh, Se H.; Lee, Kwang Hoon; Lee, Yoon Sook; Ko, Eun; Kim, Kyung Eun; Kim, Hyung Chan; Kim, Seokkyun; Song, Paul H.; Kim, Yong In; Kim, Chungho; Han, Sungwon

doi:10.1074/jbc.m114.572594

Cited by 30 publications

(22 citation statements)

References 25 publications

(40 reference statements)

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“…34 Ang-2 interacts directly with α5β1 integrins and activates downstream effectors to promote tumor migration. 35 When acting alone, Ang-2 does not induce apoptosis; however, at high concentrations of glucose, such as in diabetic retinopathy, it induces apoptosis in pericytes via α3β1 integrin signaling. 36 As seen in the ELISA experiments (Figure 2d), the physiological levels of Ang-2 may be at the 1 ng range, which contribute to NP cells survival.…”

Section: Discussionmentioning

confidence: 99%

The role of angiopoietin-2 in nucleus pulposus cells during human intervertebral disc degeneration

Wang

Liu

Song

et al. 2017

Laboratory Investigation

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Although evidence shows that intervertebral disc degeneration is generally characterized by angiogenesis, the role of angiopoietin has not been investigated. This study examined the presence of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) within the native intervertebral disc (IVD) and elucidated their functions in the regulation of nucleus pulposus (NP) cells. Initial investigation of uncultured NP tissue revealed that Ang-1 and Ang-2 were expressed by native NP cells. Ang-2 expression was significantly increased in infiltrated and degenerate samples relative to normal samples. The ratio of Ang-2/Ang-1 in tissues from patients increased markedly with increasing age and level of degeneration of the IVD. The ratio of both Ang-2/Ang-1 mRNA and protein increased over time when cells were subjected to constant pressure at 1 Mpa in vitro. Our findings indicate that Ang-2 plays a role in suppressing cell adhesion and viability, and promotes the apoptosis of NP cells and that Ang-2 can inhibit the pathways stimulated by Ang-1 and fibronectin. Ang-2 release during IVD degeneration causes higher ratio of Ang-2 to Ang-1, further inhibits NP cell viability and adhesion, promoting apoptosis by blocking PI3K/Akt signaling. The present study therefore provides new insights into the role of the angiopoietin-Tie system in the pathogenesis of IVD degeneration.

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Section: Discussionmentioning

confidence: 99%

The role of angiopoietin-2 in nucleus pulposus cells during human intervertebral disc degeneration

Wang

Liu

Song

et al. 2017

Laboratory Investigation

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“…Interaction with a 5 b 1 integrins plays a role in the adhesion, migration, and invasion of human umbilical vein endothelial cells. 66 Angiopoietin-2 null mice are born normally, but die in the first 14 days due to vascular defects and impaired inflammatory responses, 67 while overexpression of angiopoietin-2 in endothelial cells or in the dermis results in embryonic death. 64 Diabetic wound healing is characterized by a decrease in angiogenesis and granulation tissue formation.…”

Section: Patterns [Damps]mentioning

confidence: 99%

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

Zuliani-Alvarez

Midwood

2015

Advances in Wound Care

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Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing.

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“…Ang2 has been reported to stimulate focal adhesion kinase Fak phosphorylation on Tyr-397 via integrins in Tie2 low ECs and in tumour cells, thereby promoting cell migration [72,73]. As the endothelial tip cells of sprouting vessels express high levels of Ang2 and β1-integrin, but low levels of Tie2, the Ang2-integrin signalling axis may be well located to guide vessel sprouting during angiogenesis [72–74].…”

Section: Signalling Mechanisms Of the Ang–tie Systemmentioning

confidence: 99%

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

Eklund¹,

Kangas²,

2016

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Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)–Tie system is a second endothelial cell specific ligand–receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang–Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang–Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang–Tie system in vascular development and pathogenesis of vascular diseases.

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Gln-362 of Angiopoietin-2 Mediates Migration of Tumor and Endothelial Cells through Association with α5β1 Integrin

Cited by 30 publications

References 25 publications

The role of angiopoietin-2 in nucleus pulposus cells during human intervertebral disc degeneration

The role of angiopoietin-2 in nucleus pulposus cells during human intervertebral disc degeneration

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

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