The gain-of-function GLI1 transcription factor TGLI1 enhances expression of VEGF-C and TEM7 to promote glioblastoma angiogenesis
We recently discovered that truncated glioma-associated oncogene homolog 1 (TGLI1) is highly expressed in glioblastoma (GBM) and linked to increased GBM vascularity. The mechanisms underlying TGLI1-mediated angiogenesis are unclear. In this study, we compared TGLI1- with GLI1-expressing GBM xenografts for the expression profile of 84 angiogenesis-associated genes. The results showed that expression of six genes were upregulated and five were down-regulated in TGLI1-carrying tumors compared to those with GLI1. Vascular endothelial growth factor-C (VEGF-C) and tumor endothelial marker 7 (TEM7) were selected for further investigations because of their significant correlations with high vascularity in 135 patient GBMs. TGLI1 bound to both VEGF-C and TEM7 gene promoters. Conditioned medium from TGLI1-expressing GBM cells strongly induced tubule formation of brain microvascular endothelial cells, and the induction was prevented by VEGF-C/TEM7 knockdown. Immunohistochemical analysis of 122 gliomas showed that TGLI1 expression was positively correlated with VEGF-C, TEM7 and microvessel density. Analysis of NCBI Gene Expression Omnibus datasets with 161 malignant gliomas showed an inverse relationship between tumoral VEGF-C, TEM7 or microvessel density and patient survival. Together, our findings support an important role that TGLI1 plays in GBM angiogenesis and identify VEGF-C and TEM7 as novel TGLI1 target genes of importance to GBM vascularity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
|---|---|
| Enthalten in: |
Oncotarget - 6(2015), 26 vom: 08. Sept., Seite 22653-65 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Carpenter, Richard L [VerfasserIn] |
|---|
| Anmerkungen: |
Date Completed 04.08.2016 Date Revised 13.11.2018 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM250139006 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM250139006 | ||
| 003 | DE-627 | ||
| 005 | 20231224155104.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2015 xx |||||o 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0833.xml |
| 035 | |a (DE-627)NLM250139006 | ||
| 035 | |a (NLM)26093087 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Carpenter, Richard L |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The gain-of-function GLI1 transcription factor TGLI1 enhances expression of VEGF-C and TEM7 to promote glioblastoma angiogenesis |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.08.2016 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a We recently discovered that truncated glioma-associated oncogene homolog 1 (TGLI1) is highly expressed in glioblastoma (GBM) and linked to increased GBM vascularity. The mechanisms underlying TGLI1-mediated angiogenesis are unclear. In this study, we compared TGLI1- with GLI1-expressing GBM xenografts for the expression profile of 84 angiogenesis-associated genes. The results showed that expression of six genes were upregulated and five were down-regulated in TGLI1-carrying tumors compared to those with GLI1. Vascular endothelial growth factor-C (VEGF-C) and tumor endothelial marker 7 (TEM7) were selected for further investigations because of their significant correlations with high vascularity in 135 patient GBMs. TGLI1 bound to both VEGF-C and TEM7 gene promoters. Conditioned medium from TGLI1-expressing GBM cells strongly induced tubule formation of brain microvascular endothelial cells, and the induction was prevented by VEGF-C/TEM7 knockdown. Immunohistochemical analysis of 122 gliomas showed that TGLI1 expression was positively correlated with VEGF-C, TEM7 and microvessel density. Analysis of NCBI Gene Expression Omnibus datasets with 161 malignant gliomas showed an inverse relationship between tumoral VEGF-C, TEM7 or microvessel density and patient survival. Together, our findings support an important role that TGLI1 plays in GBM angiogenesis and identify VEGF-C and TEM7 as novel TGLI1 target genes of importance to GBM vascularity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a GLI1 | |
| 650 | 4 | |a TGLI1 | |
| 650 | 4 | |a VEGF-C | |
| 650 | 4 | |a angiogenesis | |
| 650 | 4 | |a glioblastoma | |
| 650 | 7 | |a GLI1 protein, human |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 650 | 7 | |a PLXDC1 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a VEGFC protein, human |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor C |2 NLM | |
| 650 | 7 | |a Zinc Finger Protein GLI1 |2 NLM | |
| 700 | 1 | |a Paw, Ivy |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Sirkisoon, Sherona |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Watabe, Kounosuke |e verfasserin |4 aut | |
| 700 | 1 | |a Debinski, Waldemar |e verfasserin |4 aut | |
| 700 | 1 | |a Lo, Hui-Wen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Oncotarget |d 2010 |g 6(2015), 26 vom: 08. Sept., Seite 22653-65 |w (DE-627)NLM199620113 |x 1949-2553 |7 nnns |
| 773 | 1 | 8 | |g volume:6 |g year:2015 |g number:26 |g day:08 |g month:09 |g pages:22653-65 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 6 |j 2015 |e 26 |b 08 |c 09 |h 22653-65 | ||