MUC4

MUC4 (mucin 4, cell surface associated) is a membrane-associated mucin that contributes to epithelial surface protection, lubrication, and cellular homeostasis in multiple tissues, including the respiratory and gastrointestinal tracts^[1]. Mechanistically, MUC4 functions not only as a structural mucosal component but also as a signaling regulator through its transmembrane β-subunit, which participates in receptor-mediated signaling pathways^[1][2]. A key biological feature of MUC4 is its interaction with the receptor tyrosine kinase HER2/ERBB2, resulting in HER2 stabilization and modulation of downstream oncogenic signaling networks associated with cell survival, proliferation, and tumor progression^[2][3]. Consequently, aberrant MUC4 expression has been reported in several epithelial malignancies, including pancreatic, ovarian, breast, lung, esophageal, and colorectal cancers, where it is frequently associated with altered tumor behavior and disease progression^[1][4]. In experimental cancer models, MUC4 promotes cellular motility, invasion, and metastatic phenotypes through HER2-dependent signaling mechanisms and related pathways regulating cell-matrix interactions^[3][5]. Compared with secreted gel-forming mucins and other membrane mucins, MUC4 is distinguished by its large extracellular α-subunit and signaling-competent β-subunit, enabling simultaneous barrier and receptor-regulatory functions^[1]. This dual structural and signaling capacity has made MUC4 a widely studied biomarker and mechanistic target in cancer biology research^[1][4]. For experimental applications, inhibition or downregulation of MUC4 has been shown to suppress tumor growth, migration, and metastatic potential in multiple cancer models, supporting its utility in studies of tumor progression and therapeutic resistance^[4][5].