PUBLICATION
BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression
- Authors
- Cohen, B., Tempelhof, H., Raz, T., Oren, R., Nicenboim, J., Bochner, F., Even, R., Jelinski, A., Eilam, R., Ben-Dor, S., Adaddi, Y., Golani, O., Lazar, S., Yaniv, K., Neeman, M.
- ID
- ZDB-PUB-200307-2
- Date
- 2020
- Source
- Life science alliance 3(4): (Journal)
- Registered Authors
- Tempelhof, Hanoch, Yaniv, Karina
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Modulating Agents/metabolism
- Animals
- Basic-Leucine Zipper Transcription Factors/genetics*
- Basic-Leucine Zipper Transcription Factors/metabolism
- Cell Line, Tumor
- Fanconi Anemia Complementation Group Proteins/genetics*
- Fanconi Anemia Complementation Group Proteins/metabolism
- Female
- Gene Expression Regulation, Developmental/genetics
- Humans
- Lymphangiogenesis/physiology
- Lymphatic Vessels/metabolism
- Mice
- Mice, Inbred C57BL
- Mice, Nude
- Morphogenesis
- Neovascularization, Physiologic/physiology*
- Signal Transduction
- Vascular Endothelial Growth Factor C/genetics*
- Vascular Endothelial Growth Factor C/metabolism
- Vascular Endothelial Growth Factor Receptor-2/genetics
- Vascular Endothelial Growth Factor Receptor-3/genetics
- Zebrafish/embryology
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 32132179 Full text @ Life Sci Alliance
Citation
Cohen, B., Tempelhof, H., Raz, T., Oren, R., Nicenboim, J., Bochner, F., Even, R., Jelinski, A., Eilam, R., Ben-Dor, S., Adaddi, Y., Golani, O., Lazar, S., Yaniv, K., Neeman, M. (2020) BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression. Life science alliance. 3(4):.
Abstract
Angiogenesis and lymphangiogenesis are key processes during embryogenesis as well as under physiological and pathological conditions. Vascular endothelial growth factor C (VEGFC), the ligand for both VEGFR2 and VEGFR3, is a central lymphangiogenic regulator that also drives angiogenesis. Here, we report that members of the highly conserved BACH (BTB and CNC homology) family of transcription factors regulate VEGFC expression, through direct binding to its promoter. Accordingly, down-regulation of bach2a hinders blood vessel formation and impairs lymphatic sprouting in a Vegfc-dependent manner during zebrafish embryonic development. In contrast, BACH1 overexpression enhances intratumoral blood vessel density and peritumoral lymphatic vessel diameter in ovarian and lung mouse tumor models. The effects on the vascular compartment correlate spatially and temporally with BACH1 transcriptional regulation of VEGFC expression. Altogether, our results uncover a novel role for the BACH/VEGFC signaling axis in lymphatic formation during embryogenesis and cancer, providing a novel potential target for therapeutic interventions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping