Suppression of lung adenocarcinoma migration through organelle alkalization by human lactoferrin – albumin fusion

FEBS Open Bio

卷:16

Research Article

Hana Nopia¹  Masahiro Kimura¹  Daisuke Kurimoto¹  Atsushi Sato¹ 

[1] School of Bioscience and Biotechnology, Tokyo University of Technology, Japan

关键词: Cancer migration;    epithelial–mesenchymal transition (EMT);    human lactoferrin–albumin fusion (hLF‐HSA);    matrix metalloproteinase 1 (MMP1);    Na/H exchanger 7 (NHE7);    organelle pH;   

DOI  :  10.1002/2211-5463.70237

 received in 2025-12-08, accepted in 2026-03-13,  发布年份 2026

来源: Wiley

【 摘 要 】

The fusion of human serum albumin with human lactoferrin (hLF‐HSA) exerts strong anti‐migratory effects in human lung adenocarcinoma cells through matrix metalloproteinase 1 (MMP1) downregulation. We demonstrate that hLF‐HSA disrupts organelle pH homeostasis via Na+/H+ exchanger 7 (NHE7) upregulation, inducing organelle alkalization in the Golgi apparatus. This organelle dysfunction alters the Golgi‐mediated secretome, leading to MMP1 downregulation and suppression of cell migration. hLF‐HSA‐induced MMP1 downregulation also reverses epithelial‐mesenchymal transition (EMT), further suppressing migration. Additionally, hLF‐HSA‐driven activation of caveolae‐mediated endocytosis (CavME) signaling downregulated MMP1 expression without NHE7 upregulation. These findings highlight that hLF‐HSA–mediated disruption of organelle pH regulation and CavME activation represents a potential strategy to suppress cancer cell migration.Impact statementThis work reveals a previously unrecognized link between organelle pH dysregulation and cancer cell migration. By identifying hLF‐HSA as a dual modulator of Golgi function and endocytic signaling, it provides a mechanistic basis for developing novel anti‐metastatic strategies targeting intracellular trafficking rather than cytotoxicity.

【 授权许可】

CC BY   
© 2026 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.