TY - JOUR T1 - BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000666 VL - 3 IS - 4 SP - e202000666 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 Y1 - 2020/04/01 UR - https://www.life-science-alliance.org/content/3/4/e202000666.abstract N2 - 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. ER -