Fig. 8

Working model of ADAMTS18 in HER2-positive mammary tumorigenesis and metastasis. ADAMTS18 is secreted by myoepithelial cells of mammary ducts and functions as an important regulator that links basement membrane (BM) and stroma extracellular matrix (ECM) alterations to HER2-positive tumor behavior. ADAMTS18 deficiency results in aberrant expression levels and distribution of some ECM molecules (e.g. LNα5, FN, and ColI) in BM and stroma, resulting in enhanced activity of integrin (Itgα3/α5/β1)-mediated PI3K/AKT, ERK, and JNK signaling activity. These alterations may increase the risk of HER2-positive mammary tumorigenesis and metastasis. (Cartoon picture was created with BioRender.com)