Most TTF-1-negative pulmonary adenocarcinomas are mucinous lesions with the predominant expression of MUC5AC.

ERK kinase activation is necessary for the regulation of epidermal growth factor receptor (EGFR)-mediated MUC5AC expression by Notch signaling in a lung carcinoma cell line.

MUC5AC interacts with integrin beta4 that mediates phosphorylation of FAK at Y397 leading to lung cancer cell migration.

Study in 2 independent human cohorts found at both mRNA and protein levels that MUC5AC is a significant determinant of poor prognoses in patients with KRAS (but not EGFR) mutant lung adenocarcinoma.

MUC5AC was an independent prognosis factor for poor prognosis in lung adenocarcinoma with mucin production. MUC5AC was associated with lymphovascular invasion and tumors with intra-cytoplasmic mucin. MUC5AC was more significant in invasive mucinous adenocarcinoma, as well as in tumors with KRAS mutations and a lack of thyroid transcription factor 1 expression.

Study using mice with lung adenocarcinoma induced chemically with urethane or transgenically by mutant-Kras expression observed significantly reduced tumor development in animals lacking Muc5ac compared with controls.