Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular abnormality

Kim, Il-Kug; Kim, Kangsan; Lee, Eunhyeong; Oh, Dong Sun; Park, Chan Soon; Park, Seong Yeol; Yang, Jae‐Ho; Kim, Ju Hee; Kim, Hyung Seok; Shima, David T.; Kim, Jeong Hoon; Hong, Seok Ho; Cho, Young Hyun; Kim, Young Hoon; Park, Jong Bae; Koh, Gou Young; Ju, Youngseok; Lee, Kyung-Mi; Lee, Seung-Joo; Kim, Injune

doi:10.1084/jem.20170123

Cited by 37 publications

(35 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14G-L). Consistent with previous reports in the literature [27][28][29]44,45 we find that p-AKT and p-ERK1/2 are more strongly activated in tumor-associated blood vessels than in the surrounding tumor tissue, although longer-exposure images confirm that p-AKT and p-ERK1/2 are indeed also present in the surrounding tumor cells ( Supplementary Fig. 14M, N).…”

Section: Resultssupporting

confidence: 92%

Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling

et al. 2020

View full text Add to dashboard Cite

Anti-angiogenic therapies have generated significant interest for their potential to combat tumor growth. However, tumor overproduction of pro-angiogenic ligands can overcome these therapies, hampering success of this approach. To circumvent this problem, we target the resynthesis of phosphoinositides consumed during intracellular transduction of proangiogenic signals in endothelial cells (EC), thus harnessing the tumor's own production of excess stimulatory ligands to deplete adjacent ECs of the capacity to respond to these signals. Using zebrafish and human endothelial cells in vitro, we show ECs deficient in CDPdiacylglycerol synthase 2 are uniquely sensitive to increased vascular endothelial growth factor (VEGF) stimulation due to a reduced capacity to re-synthesize phosphoinositides, including phosphatidylinositol-(4,5)-bisphosphate (PIP2), resulting in VEGF-exacerbated defects in angiogenesis and angiogenic signaling. Using murine tumor allograft models, we show that systemic or EC specific suppression of phosphoinositide recycling results in reduced tumor growth and tumor angiogenesis. Our results suggest inhibition of phosphoinositide recycling provides a useful anti-angiogenic approach.

show abstract

Section: Resultssupporting

confidence: 92%

Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling

et al. 2020

View full text Add to dashboard Cite

show abstract

“…16 Sox7 and Sox17 are closely associated various types of angiogenesis. [8][9][10][11]13,17 This is the first report of the proangiogenic role of Sox7 and Sox17 in wound healing. The present results show that these two transcription factors are upregulated in ECs during wound angiogenesis.…”

Section: Discussionmentioning

confidence: 72%

“…Depending on the context, Sox7 and Sox17 may affect the expression of each other. 8,9,13 As Sox7/ Sox17 double deletion markedly influenced vascularity in the wound tissue in comparison with the individual deletion of either protein, and each transcription factor was predicted to play an independent role. To confirm this, their respective effects on each other were investigated.…”

Section: Loss Of Sox7 or Sox17 Does Not Affect The Expression Of Eachmentioning

confidence: 99%

“…Recently, studies on developmental and tumor angiogenesis have focused on the proangiogenic transcription factors Sox7 and Sox17 and their related signaling pathways. [8][9][10][11] Both transcription factors display endothelial cell (EC)-specific expression in developing and tumor vessels and their deletion inhibits angiogenesis. Accordingly, studies on the role of Sox7 and Sox17 in angiogenesis will improve the understanding of the transcriptional regulation of angiogenesis not only in developmental or tumor vessels but also in other types of angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dll4 Blockade Promotes Angiogenesis in Nonhealing Wounds of Sox7-Deficient Mice

Yang

Ryu

Kim

et al. 2020

Advances in Wound Care

Self Cite

View full text Add to dashboard Cite

Objective: This study aimed to elucidate the role of the proangiogenic transcription factors Sox7 and Sox17 in the wound healing process and investigate the therapeutic potential of Dll4 blockade, which is an upstream regulator of Sox17, for the treatment of nonhealing wounds. Approach: After generating a full-thickness skin defect wound model of endothelial Sox7-and/or Sox17-deficient mice, we measured the wound healing rates and performed histological analysis. The effects of an anti-Dll4 antibody on wound angiogenesis in Sox7-deficient mice and db/db diabetic mice were assessed. Results: Sox7 and/or Sox17 deletion delayed wound healing. Moreover, the loss of Sox7 and Sox17 inhibited wound angiogenesis, without affecting the expression of the other. Of interest, after anti-Dll4 antibody treatment, Sox17 levels were increased and the suppression of angiogenesis was alleviated in Sox7-deficient mice and db/db diabetic mice. Consequently, Dll4 blockade effectively recovered the observed delay in wound healing. Innovation: The proangiogenic role of Sox7 and Sox17 in wound angiogenesis was addressed and effective treatment of nonhealing wounds by Dll4 blockade was suggested. Conclusion: This study revealed the proangiogenic role of the transcription factors Sox7 and Sox17 in wound angiogenesis. Furthermore, we suggest a novel method for treating nonhealing wounds by particularly targeting the Dll4-Sox17 axis.

show abstract

“…In addition to effects on tumor cell functionalities, hypoxia greatly impacts TMEs in various respects [179,237]. Unlike the vasculature that is facilitated by the FN deposited in TMEs where nutrients and oxygen are properly provided under normoxia, the neovascular system provoked by HIF-upregulated VEGF under hypoxic conditions is, although abundant, highly abnormal with poor integrity [238][239][240]. Provided that FN deposited in the ECM within TMEs supports a better perfused vasculature and thus promotes rapid tumor growth under normoxia, whether the hypoxia-induced disintegrated vasculature is attributable in part to a FN-deficient ECM remains unclear and is worth investigating.…”

Section: Hypoxia-induced Reexpression Of Fn In Tumor Cells and Cancermentioning

confidence: 99%

Fibronectin in Cancer: Friend or Foe

Lin

Yang

et al. 2019

Cells

134

117

View full text Add to dashboard Cite

The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies. Figure 1. (A) The structure of fibronectin (FN) containing three types of repeats and three alternative splicing regions (EDA, EDB, and IIICS) with several well-known binding sites for extracellular matrix (ECM) components (fibrin, heparin, collagen, and gelatin), polymeric assembly (FN-FN), cell adhesion (integrin α5β1), DPP IV, and two C-terminal disulfide bonds for dimeric FN. (B) Publications in recent some forty years regarding the roles of cancerous FN and stromal FN in ECM in tumor progression as represented in a time-line pattern. Among 26 publications before 2000, 15 (57.7%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 3 (11.5%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 8 (30.8%) papers are related to the role of stromal FN in promoting early tumor progression but not late metastasis (in dark green boxes). On the contrary, Among 46 publications after 2000, 7 (15.2%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 25 (54.4%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 14 (30.4%) papers are related to the role of stromal FN in promoting early tumor progression but not late metastasis (in dark green boxes). Abbreviations in boxes are referred to the context of this article. (C) Percentages of articles for the three various roles of FN (the same colors as depicted in (B) before 2000 and after 2000. Numbers in the parenthesis represent article numbers. The Pathobiology of CancerFigure 1. (A) The structure of fibronectin (FN) containing three types of repeats and three alternative splicing regions (EDA, EDB, and IIICS) with several well-known binding sites for extracellular matrix (ECM) components (fibrin, heparin, collagen, and gelatin), polymeric assembly (FN-FN), cell adhesion (integrin α5β1), DPP IV, and two C-terminal disulfide bonds for dimeric FN. (B) Publications in recent some forty years regarding the roles of cancerous FN and stromal FN in ECM in tumor progression as represented in a time-line pattern. Among 26 publications before 2000, 15 (57.7%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 3 (11.5%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 8 (30.8%) papers are related to the r...

show abstract

Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular abnormality

Cited by 37 publications

References 57 publications

Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling

Anti-angiogenic effects of VEGF stimulation on endothelium deficient in phosphoinositide recycling

Dll4 Blockade Promotes Angiogenesis in Nonhealing Wounds of Sox7-Deficient Mice

Fibronectin in Cancer: Friend or Foe

Contact Info

Product

Resources

About