Soluble E-cadherin (sEcad)

Soluble E-cadherin (sEcad) is an 80-kDa truncated extracellular fragment of the E-cadherin (CDH1) protein, generated through proteolytic shedding of the full-length transmembrane molecule by enzymes such as ADAM10, ADAM17, and various matrix metalloproteinases (MMPs) [4.2.3, 4.3.2]. While membrane-bound E-cadherin is a well-characterized tumor suppressor that maintains epithelial cell-cell adhesion, the shed soluble form (sEcad) acts as a potent pro-oncogenic factor in the tumor microenvironment [4.2.1, 4.2.5]. sEcad functions as a ligand that can bind and activate receptor tyrosine kinases, including HER2 and HER3, thereby stimulating downstream pathways like PI3K/Akt and MAPK that promote cell survival and proliferation [6.1.1, 6.1.5]. Recent research has identified sEcad as a novel driver of brain metastasis, particularly in inflammatory breast cancer (IBC), where it activates the NF-κB signaling pathway and the CXCL1-CXCR2 axis to induce an inflammatory microenvironment and resistance to anoikis [4.2.3, 4.2.4]. Therapeutic strategies targeting sEcad include the development of fragment-specific monoclonal antibodies (e.g., DECMA-1), inhibitors of the shedding proteases (e.g., ADAM10 inhibitors), and antagonists of its downstream signaling partners like CXCR2 and PDIA4 [5.1.3, 6.1.1, 6.1.4].

Other names

sE-cad80 kDa E-cadherin fragmentE-cadherin ectodomainSoluble Cadherin-1Truncated E-cadherin

Neutralization of the soluble fragment to prevent interaction with receptor tyrosine kinases (e.g., HER2/HER3); inhibition of proteolytic shedding by ADAM10/17 or MMPs; inhibition of downstream signaling axes such as CXCL1-CXCR2 or PDIA4-mediated pathways.