title: SRF selectively controls tip cell invasive behavior in angiogenesis.
abstract: Efficient angiogenic sprouting is essential for embryonic, postnatal and tumor development. Serum response factor (SRF) is known to be important for embryonic vascular development. Here, we studied the effect of inducible endothelial-specific deletion of Srf in postnatal and adult mice. We find that endothelial SRF activity is vital for postnatal growth and survival, and is equally required for developmental and pathological angiogenesis, including during tumor growth. Our results demonstrate that SRF is selectively required for endothelial filopodia formation and cell contractility during sprouting angiogenesis, but seems dispensable for vascular remodeling. At the molecular level, we observe that vascular endothelial growth factor A induces nuclear accumulation of myocardin-related transcription factors (MRTFs) and regulates MRTF/SRF-dependent target genes including Myl9, which is important for endothelial cell migration in vitro. We conclude that SRF has a unique function in regulating migratory tip cell behavior during sprouting angiogenesis. We hypothesize that targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth.
authors.affiliation: UPMC Univ Paris 06, UR 4, Aging, Stress and Inflammation, 75005 Paris, France. claudio.franco@cancer.org.uk
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Franco
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Blanc
authors.forename: Ara
authors.initials: A
authors.lastname: Parlakian
authors.forename: Raquel
authors.initials: R
authors.lastname: Blanco
authors.forename: Irene M
authors.initials: IM
authors.lastname: Aspalter
authors.forename: Natalia
authors.initials: N
authors.lastname: Kazakova
authors.forename: Nicolas
authors.initials: N
authors.lastname: Diguet
authors.forename: Elena
authors.initials: E
authors.lastname: Mylonas
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gao-Li
authors.forename: Anne
authors.initials: A
authors.lastname: Vaahtokari
authors.forename: Virgine
authors.initials: V
authors.lastname: Penard-Lacronique
authors.forename: Markus
authors.initials: M
authors.lastname: Fruttiger
authors.forename: Ian
authors.initials: I
authors.lastname: Rosewell
authors.forename: Mathias
authors.initials: M
authors.lastname: Mericskay
authors.forename: Holger
authors.initials: H
authors.lastname: Gerhardt
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D009218:Myosins / Q000378:metabolism; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011554:Pseudopodia / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012171:Retinal Vessels / Q000196:embryology* / Q000473:pathology; D026362:Serum Response Factor / Q000378:metabolism / Q000502:physiology*
chemical_list: D000199:Actins; D034741:RNA, Small Interfering; D026362:Serum Response Factor; D009218:Myosins
keywords: Actin; Filopodia; Mouse; Myosin; SRF; Sprouting angiogenesis