BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression.

Life Science Alliance
Batya CohenMichal Neeman

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.

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Datasets Mentioned

BETA
BC057894.1

Methods Mentioned

BETA
xenograft
transgenic
FACS
electrophoresis
PCR
genotyping
xenografts
immunoprecipitation
RNA-Seq
antisense oligonucleotides

Software Mentioned

Genomatix Genome Analyzer
Promoters Clusters
Adobe Photoshop
Genomatix Genome Analyzer MatInspector
Genomatix
MatInspector
Statistix
Panoramic Viewer
ImageJ
Image Pro Plus

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