RT Journal Article
SR Electronic
T1 BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000666
DO 10.26508/lsa.202000666
VO 3
IS 4
A1 Batya Cohen
A1 Hanoch Tempelhof
A1 Tal Raz
A1 Roni Oren
A1 Julian Nicenboim
A1 Filip Bochner
A1 Ron Even
A1 Adam Jelinski
A1 Raya Eilam
A1 Shifra Ben-Dor
A1 Yoseph Adaddi
A1 Ofra Golani
A1 Shlomi Lazar
A1 Karina Yaniv
A1 Michal Neeman
YR 2020
UL https://www.life-science-alliance.org/content/3/4/e202000666.abstract
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.