PT  - JOURNAL ARTICLE
AU  - Batya Cohen
AU  - Hanoch Tempelhof
AU  - Tal Raz
AU  - Roni Oren
AU  - Julian Nicenboim
AU  - Filip Bochner
AU  - Ron Even
AU  - Adam Jelinski
AU  - Raya Eilam
AU  - Shifra Ben-Dor
AU  - Yoseph Adaddi
AU  - Ofra Golani
AU  - Shlomi Lazar
AU  - Karina Yaniv
AU  - Michal Neeman
TI  - BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression
AID  - 10.26508/lsa.202000666
DP  - 2020 Apr 01
TA  - Life Science Alliance
PG  - e202000666
VI  - 3
IP  - 4
4099  - https://www.life-science-alliance.org/content/3/4/e202000666.short
4100  - https://www.life-science-alliance.org/content/3/4/e202000666.full
SO  - Life Sci. Alliance2020 Apr 01; 3
AB  - 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.