Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension

Ye, Zhongde; Zhang, Chun Xia; Tu, Tao; Sun, Min; Liú, Dan; Lu, Di; Feng, Jing; Yang, Di; Liu, Feng; Yan, Xiyun

doi:10.1038/ncomms3803

Cited by 72 publications

(69 citation statements)

References 49 publications

(64 reference statements)

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“…Laminin-421 could also be such a ligand because we have detected LMα4 epitopes on the surface of melanoma cells (unpublished data). Most recently, Wnt5a was reported to use MCAM (CD146) as a receptor to regulate cell motility (Ye et al, 2013). This novel finding may reflect a functional link between α4-laminins and Wnt5a in cell migration.…”

Section: Discussionmentioning

confidence: 96%

Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146)

et al. 2014

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α4-laminins, such as laminins 411 and 421, are mesenchymal laminins expressed by blood and lymphatic vessels and some tumor cells. Laminin-411 promotes migration of leukocytes and endothelial cells, but the effect of this laminin and laminin-421 on tumor cells is poorly understood. In the present study, we demonstrate that laminin-411 and, to a greater extent, laminin-421 significantly promote migration of tumor cells originated from melanomas, gliomas and different carcinomas via α6β1 integrin. In solid-phase binding assays, both laminins similarly bound α6β1 integrin but only laminin-421, among several laminin isoforms, readily bound MCAM (CD146), a cell-surface adhesion molecule strongly associated with tumor progression. Accordingly, a function-blocking mAb to MCAM inhibited tumor cell migration on laminin-421 but not on laminins 411 or 521. In tumor tissues, melanoma cells co-expressed MCAM, laminin α4, β1, β2 and γ1 chains, and integrin α6 and β1 chains. The present data highlight the novel role of α4-laminins in tumor cell migration and identify laminin-421 as a primary ligand for MCAM and a putative mediator of tumor invasion and metastasis.

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Section: Discussionmentioning

confidence: 96%

Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146)

et al. 2014

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“…Indeed, our present study demonstrates that CD146 is a receptor for netrin-1 to promote developmental angiogenesis. Moreover, CD146 acts as a receptor for Wnt5a to regulate cell motility and convergent extension 26 , and Wnt signaling has been reported to contribute to angiogenesis as well 47,48 . The schematic of CD146 involved, angiogenesis-related pathways is shown in Supplementary information, Figure S8.…”

Section: Discussionmentioning

confidence: 99%

“…It contains five Ig-like domains in its extracellular region, a single transmembrane domain and a cytoplasmic tail 23 . As a multi-functional molecule, CD146 participates in various biological processes including angiogenesis, tumor metastasis, lymphocyte activation, morphogenesis during development and tissue regeneration 24,25,26 . Expressed on endothelial cells, CD146 is required for endothelial cell proliferation, migration and tube formation 27,28 , playing critical roles in angiogenesis 29,30,31,32 .…”

Section: Introductionmentioning

confidence: 99%

CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development

et al. 2015

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Angiogenesis, a process that newly-formed blood vessels sprout from pre-existing ones, is vital for vertebrate development and adult homeostasis. Previous studies have demonstrated that the neuronal guidance molecule netrin-1 participates in angiogenesis and morphogenesis of the vascular system. Netrin-1 exhibits dual activities in angiogenesis: either promoting or inhibiting angiogenesis. The anti-angiogenic activity of netrin-1 is mediated by UNC5B receptor. However, how netrin-1 promotes angiogenesis remained unclear. Here we report that CD146, an endothelial transmembrane protein of the immunoglobulin superfamily, is a receptor for netrin-1. Netrin-1 binds to CD146 with high affinity, inducing endothelial cell activation and downstream signaling in a CD146-dependent manner. Conditional knockout of the cd146 gene in the murine endothelium or disruption of netrin-CD146 interaction by a specific anti-CD146 antibody blocks or reduces netrin-1-induced angiogenesis. In zebrafish embryos, downregulating either netrin-1a or CD146 results in vascular defects with striking similarity. Moreover, knocking down CD146 blocks ectopic vascular sprouting induced by netrin-1 overexpression. Together, our data uncover CD146 as a previously unknown receptor for netrin-1 and also reveal a functional ligand for CD146 in angiogenesis, demonstrating the involvement of netrin-CD146 signaling in angiogenesis during vertebrate development.

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“…These cells differ from cytotrophoblasts by expression of some endothelial genes, such as adhesion molecule MCAM (Jouve et al 2013;Kaspi et al 2013), lowered E-cadherin (CDH1) (Zhou et al 1997), and the receptor for vascular endothelial growth factor FLT1. Note that MCAM may be a receptor for WNT5A, affecting cell motility (Ye et al 2013). While EVTs are involved in invasion in early pregnancy (Bischof et al 2000), some of the invasion-associated signature may be lacking at term (Ji et al 2013).…”

Section: Extravillous Trophoblast (Evt; Cluster 5)mentioning

confidence: 99%

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

et al. 2017

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Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types. We find a highly cell-type-specific expression of G-protein-coupled receptors, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a large number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, and suggest a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast.

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Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension

Cited by 72 publications

References 49 publications

Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146)

Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146)

CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface

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