TY - JOUR
T1 - BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression
AU - Cohen, Batya
AU - Tempelhof, Hanoch
AU - Raz, Tal
AU - Oren, Roni
AU - Nicenboim, Julian
AU - Bochner, Filip
AU - Even, Ron
AU - Jelinski, Adam
AU - Eilam, Raya
AU - Ben-Dor, Shifra
AU - Adaddi, Yoseph
AU - Golani, Ofra
AU - Lazar, Shlomi
AU - Yaniv, Karina
AU - Neeman, Michal
N1 - 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/).
PY - 2020/3/4
Y1 - 2020/3/4
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85081330078&partnerID=8YFLogxK
U2 - 10.26508/LSA.202000666
DO - 10.26508/LSA.202000666
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 32132179
AN - SCOPUS:85081330078
SN - 2575-1077
VL - 3
JO - Life Science Alliance
JF - Life Science Alliance
IS - 4
M1 - LSA.202000666
ER -
