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ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters

หน่วยงาน Nanyang Technological University, Singapore

รายละเอียด

ชื่อเรื่อง : ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters
นักวิจัย : Huang, Royston-Luke , Teo, Ziqiang , Chong, Han Chung , Zhu, Pengcheng , Tan, Ming Jie , Tan, Chek Kun , Lam, Ivan Chee Ren , Sng, Ming Keat , Leong, David Tai Wei , Tan, Suet Mien , Kersten, Sander , Ding, Jeak Ling , Li, Hoi-Yeung , Tan, Nguan Soon
คำค้น : DRNTU::Science::Biological sciences::Molecular biology.
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2554
อ้างอิง : Huang, R. L., Teo, Z., Chong, H. C., Zhu, P., Tan, M. J., Tan, C. K., et al. (2011). ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters. Blood, 118, 3990-4002. , http://hdl.handle.net/10220/7264 , http://dx.doi.org/10.1182/blood-2011-01-328716 , 161430
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Blood
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Vascular disruption induced by interactions between tumor-secreted permeability factors and adhesive proteins on endothelial cells facilitates metastasis. The role of tumor-secreted angiopoietin-like 4 (cANGPTL4) in vascular leakiness and metastasis is controversial due to the lack of understanding of how cANGPTL4 modulates vascular integrity. Here, we show that cANGPTL4 instigated the disruption of endothelial continuity by directly interacting with three novel binding partners, integrin α5β1, VE-cadherin and claudin-5, in a temporally sequential manner, thus facilitating metastasis. We showed that cANGPTL4 binds and activates integrin α5β1-mediated Rac1/PAK signaling to weaken cell-cell contacts. cANGPTL4 subsequently associated with and declustered VE-cadherin and claudin-5, leading to endothelial disruption. Interfering with the formation of these cANGPTL4 complexes delayed vascular disruption. In vivo vascular permeability and metastatic assays performed using ANGPTL4-knockout and wild-type mice injected with either control or ANGPTL4-knockdown tumors confirmed that cANGPTL4 induced vascular leakiness and facilitated lung metastasis in mice. Thus, our findings elucidate how cANGPTL4 induces endothelial disruption. Our findings have direct implications for targeting cANGPTL4 to treat cancer and other vascular pathologies.

บรรณานุกรม :
Huang, Royston-Luke , Teo, Ziqiang , Chong, Han Chung , Zhu, Pengcheng , Tan, Ming Jie , Tan, Chek Kun , Lam, Ivan Chee Ren , Sng, Ming Keat , Leong, David Tai Wei , Tan, Suet Mien , Kersten, Sander , Ding, Jeak Ling , Li, Hoi-Yeung , Tan, Nguan Soon . (2554). ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Huang, Royston-Luke , Teo, Ziqiang , Chong, Han Chung , Zhu, Pengcheng , Tan, Ming Jie , Tan, Chek Kun , Lam, Ivan Chee Ren , Sng, Ming Keat , Leong, David Tai Wei , Tan, Suet Mien , Kersten, Sander , Ding, Jeak Ling , Li, Hoi-Yeung , Tan, Nguan Soon . 2554. "ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Huang, Royston-Luke , Teo, Ziqiang , Chong, Han Chung , Zhu, Pengcheng , Tan, Ming Jie , Tan, Chek Kun , Lam, Ivan Chee Ren , Sng, Ming Keat , Leong, David Tai Wei , Tan, Suet Mien , Kersten, Sander , Ding, Jeak Ling , Li, Hoi-Yeung , Tan, Nguan Soon . "ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2554. Print.
Huang, Royston-Luke , Teo, Ziqiang , Chong, Han Chung , Zhu, Pengcheng , Tan, Ming Jie , Tan, Chek Kun , Lam, Ivan Chee Ren , Sng, Ming Keat , Leong, David Tai Wei , Tan, Suet Mien , Kersten, Sander , Ding, Jeak Ling , Li, Hoi-Yeung , Tan, Nguan Soon . ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2554.