Hippo-YAP/TAZ signaling in angiogenesis

Park, Jeong Ae; Kwon, Young Guen

doi:10.5483/bmbrep.2018.51.3.016

Cited by 63 publications

(45 citation statements)

References 49 publications

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“…The inhibition of the formation of FAs and F-actin stress fibers that we report here appears as the most conceivable mechanism by which LPHN2 negatively regulates YAP/TAZ signaling in ECs. In agreement with what previously reported [reviewed in (Park & Kwon, 2018)], the aberrant hyperactivation of YAP/TAZ caused by lphn2a knockdown in zebrafish embryos is associated with TJ disarrangement in blood vessel ECs. Our data show that, likely due to the loosening of endothelial intercellular adhesions, the lack of Lphn2a might favor tumor melanoma cells extravasation.…”

Section: Resultssupporting

confidence: 93%

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion

Camillo

Facchinello

Villari

et al. 2020

Preprint

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Dynamic modulation of endothelial cell (EC) adhesion to extracellular matrix (ECM) in response to mechanostimuli is essential for blood vessel patterning and functioning. Yet, the molecular mechanisms involved in this biological process are far to be completely deciphered. Here, we identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of vascular morphogenesis and endothelial barrier function. In cultured ECs, endogenous LPHN2 localizes at ECM adhesions, signals through cAMP/Rap1, and, via its fibronectin-leucine-rich transmembrane (FLRT)-binding domain, negatively regulates ECM-elicited haptotaxis. ECs also express endogenous FLRT2 ligand that promotes cAMP/Rap1 signaling and hinders haptotaxis in a LPHN2-dependent manner. Vascular ECs of lphn2a knock-out zebrafish embryos become abnormally stretched, display a hyperactive Hippo mechanosensing pathway, and lack proper intercellular junctions. Indeed, intravascularly injected cancer cells extravasate more easily in lphn2a null animals. Thus, LPHN2 ligands, such as FLRT2, may be therapeutically exploited to interfere with cancer metastatic dissemination.

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Section: Resultssupporting

confidence: 93%

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion

Camillo

Facchinello

Villari

et al. 2020

Preprint

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“…For instance, sphingosine-1-phosphate [S1P activates the S1P receptor, which in turn activates Rac], increases the formation of junction protrusions (both JAIL and lamellipodia) and improves barrier function (Mehta et al, 2005;Tauseef et al, 2008;Breslin et al, 2015;Cao et al, 2017). Furthermore, signaling through YAP/TAZ proteins (Totaro et al, 2018), the transcriptional co-activators of the Hippo signaling pathway involved in growth control and in cardiovascular development and diseases (Huang et al, 2005;He et al, 2018;Park and Kwon, 2018), has been demonstrated to be important in this process, as YAP/TAZ depletion reduced the formation of JAIL (Giampietro et al, 2015;Neto et al, 2018). It is reasonable to assume that signals that modulate the organization and dynamics of EC junctions, such as the vascular phosphotyrosine phosphatase (VE-PTP; also known as PTPRB), which binds to VE-cadherin and thus might be able to control VE-cadherin cluster formation through phosphorylation (Nawroth et al, 2002;Hayashi et al, 2013), VEGFR1 (Cao, 2009) and Angiopoetin-Tie signaling, 1) Decrease in Rel-VEcad-C 2) VE-cadherin cluster can be arranged and distributed as: -linear (Rel-VEcad-C can be low or high) -interrupted -reticular -as plaques (result of JAIL) -as membrane invaginations (?…”

Section: Molecular Control Of Jailmentioning

confidence: 99%

Putting VE-cadherin into JAIL for junction remodeling

Cao

Schnittler

2019

Journal of Cell Science

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Junction dynamics of endothelial cells are based on the integration of signal transduction, cytoskeletal remodeling and contraction, which are necessary for the formation and maintenance of monolayer integrity, but also enable repair and regeneration. The VE-cadherincatenin complex forms the molecular basis of the adherence junctions and cooperates closely with actin filaments. Several groups have recently described small actin-driven protrusions at the cell junctions that are controlled by the Arp2/3 complex, contributing to cell junction regulation. We identified these protrusions as the driving force for VE-cadherin dynamics, as they directly induce new VE-cadherin-mediated adhesion sites, and have accordingly referred to these structures as junction-associated intermittent lamellipodia (JAIL). JAIL extend over only a few microns and thus provide the basis for a subcellular regulation of adhesion. The local (subcellular) VE-cadherin concentration and JAIL formation are directly interdependent, which enables autoregulation. Therefore, this mechanism can contribute a subcellularly regulated adaptation of cell contact dynamics, and is therefore of great importance for monolayer integrity and relative cell migration during wound healing and angiogenesis, as well as for inflammatory responses. In this Review, we discuss the mechanisms and functions underlying these actin-driven protrusions and consider their contribution to the dynamic regulation of endothelial cell junctions.

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“…Therefore, novel therapeutic approaches are required to improve outcomes for ovarian cancer patients. Angiogenesis refers to the formation of new blood vessels from pre-existing endothelium, a physiological process that is vital for tissue repair and development (5,6). In pathological states such as cancer, angiogenesis is a fundamental process that supplies tumors with oxygen and nutrition required for their growth and survival (Fig.…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis and vasculogenic mimicry as therapeutic targets in ovarian cancer

Lim

Kwon

et al. 2020

BMB Rep.

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Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer. [

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Hippo-YAP/TAZ signaling in angiogenesis

Cited by 63 publications

References 49 publications

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion

LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion

Putting VE-cadherin into JAIL for junction remodeling

Angiogenesis and vasculogenic mimicry as therapeutic targets in ovarian cancer

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