BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression

Batya Cohen, Hanoch Tempelhof, Tal Raz, Roni Oren, Julian Nicenboim, Filip Bochner, Ron Even, Adam Jelinski, Raya Eilam, Shifra Ben-Dor, Yoseph Adaddi, Ofra Golani, Shlomi Lazar, Karina Yaniv*, Michal Neeman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageAmerican English
Article numberLSA.202000666
JournalLife Science Alliance
Volume3
Issue number4
DOIs
StatePublished - 4 Mar 2020

Bibliographical note

Publisher Copyright:
© License: This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

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