New insights into the role of soluble E-cadherin in tumor angiogenesis

Cell Stress

Philip P. Ip¹  Alice S.T. Wong²  Maggie K.S. Tang² 

[1] Department of Pathology, University of Hong Kong, Pokfulam Road, Hong Kong.;School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong.;

关键词: soluble E-cadherin;    ovarian carcinoma;    angiogenesis;    exosome;    β-catenin;    NFκB;   

DOI  :  10.15698/cst2018.09.154

来源: DOAJ

【 摘 要 】

A key to successful metastasis is the formation of new vasculature, known as angiogenesis. Therefore, it is of great interest to unravel the underlying molecular mechanisms of tumor angiogenesis. Cadherins are a major class of cell surface receptors. The loss of cadherins, especially E-cadherin, is a well-established marker for tumor metastasis. Loss of E-cadherin is also a defining characteristic of several carcinomas, such as lobular carcinoma of the breast, and de-differentiated endometrioid carcinoma of the endometrium and ovary, which are known to be associated with more aggressive tumor behavior. Although E-cadherin is synthesized as a transmembrane molecule, its extracellular domain can be enzymatically cleaved off and released as a soluble E-cadherin (sE-cad), and this accounts for the loss of E-cadherin function or expression that has been implicated in tumor progression and metastasis. Importantly, sE-cad is present at high levels in the serum and malignant ascites of ovarian carcinoma patients. Nevertheless, little is known about how this essential protein dictates metastasis. Hitherto, many studies have given attention only to the dominant negative role of the loss of E-cadherin in weakening cell-cell adhesion, however, it is not known if sE-cad has biological activity in itself. In addition, the release mechanism of sE-cad has remained elusive. Here we show for the first time that sE-cad is a pivotal regulator of angiogenesis. We further show that exosomes are a novel major platform for the cleavage and release of sE-cad in vitro, in vivo and in patients’ derived samples (Nat Commun, 9: 2270).

【 授权许可】

Unknown