Abstract
MUC14/Endomucin, a transmembrane mucin, is a potential prognostic biomarker in malignancies. This study aimed to elucidate the functional impact of MUC14 on tumor proliferation, migration, immune microenvironment modulation, and cisplatin response in lung adenocarcinoma (LUAD), and investigate its molecular mechanisms. LUAD cell lines with MUC14 overexpression (MUC14-OE) or silencing were constructed. Malignant behaviors were assessed via CCK-8, Transwell, and colony formation assays. Immune cell infiltration was quantified by CD3+/CD8 + immunohistochemistry. Subcutaneous xenograft and tail-vein metastasis murine models evaluated in vivo tumor progression and cisplatin responsiveness. Mechanisms were characterized using FRET and western blotting. Multiplatform bioinformatics analysis of public databases correlated MUC14 expression with clinical outcomes, immune infiltration, and chemotherapy response. MUC14-OE inhibited LUAD cell proliferation, migration, colony formation, and adhesion, while silencing promoted these phenotypes. MUC14 expression positively correlated with CD3+/CD8 + T-cell infiltration. In vivo, MUC14-OE suppressed subcutaneous tumor growth, lung metastasis, and enhanced cisplatin efficacy. Mechanistically, MUC14 inhibited integrin α8β6 clustering, suppressing PI3K/AKT and MAPK/ERK signaling. Cisplatin sensitization involved JNK/c-Jun pathway activation. This study establishes MUC14 as a multifunctional tumor suppressor in LUAD. It inhibits integrin α8β6-mediated PI3K/AKT and MAPK/ERK signaling to suppress tumor growth, promotes CD8+ T-cell infiltration, and augments cisplatin sensitivity via the JNK/c-Jun pathway. These findings nominate MUC14 as a prognostic biomarker and therapeutic target, suggesting combinatorial strategies integrating immunotherapy and chemotherapy.
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The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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We thank all who help us in writing the manuscript.
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This study was supported by 2023 Basic scientific research expenses for scientific research projects of universities of Heilongjiang province (No.2023-KYYWF-0182).
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X.L. performed the literature search, in vitro experiments and drafted the manuscript. S.H. was responsible for the in vivo studies. M.L., Z.Z. and C.X. assisted with specific in vitro assays. S.Y. and G.H. designed concept of the study and revised the whole manuscript. All authors have read and agreed to the published version of the manuscript.
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This study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (YJSKY2023-264). Informed consent was obtained from all individual participants and/or their legal guardians. All procedures followed were in accordance with the ethical standards approved by the Institutional Ethics Committee on human experimentation and with the Helsinki Declaration. The animal study protocol (YJSDW2023-233) was approved by the same Medical Ethics Committee of the Second Affiliated Hospital of Harbin Medical University, and was conducted in accordance with the National Institutes of Health guide for the care and use of Laboratory animals. This study is reported in accordance with the ARRIVE guidelines 2.0.
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Li, X., Li, M., Huang, S. et al. MUC14 suppresses lung adenocarcinoma via integrin α8β6/PI3K/AKT/MAPK modulating cisplatin response and immunity. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39019-z
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DOI: https://doi.org/10.1038/s41598-026-39019-z
