Work

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

Year: 2026

Type: article

Abstract: 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 statement This 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.

Source: FEBS Open Bio

DOI: 10.1002/2211-5463.70237

Authors: Hana Nopia, Masahiro Kimura, Daisuke Kurimoto, Atsushi Sato

Institution: Tokyo University of Technology

Language: English

Topic: Protease and Inhibitor Mechanisms

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,210