Human Lactoferrin/Human Serum Albumin Fusion Protein Strongly Inhibits Cancer Cell Migration Related to Cancer Metastasis by Disrupting Golgi pH Homeostasis in Cancer Cells
A research group at Tokyo University of Technology discovered that a fusion protein of human lactoferrin and human serum albumin (hLF-HSA) strongly inhibits cancer cell migration by disrupting Golgi pH homeostasis. This finding is expected to lead to the development of new drug discovery strategies and was published in the international scientific journal "FEBS Open Bio" on March 24, 2026.
📋 Article Processing Timeline
- 📰 Published: March 30, 2026 at 19:30
- 🔍 Collected: March 30, 2026 at 22:56 (3h 26m after Published)
- 🤖 AI Analyzed: April 22, 2026 at 22:41 (551h 45m after Collected)
A research group including Hana Nopia (doctoral student), Assistant Professor Masahiro Kimura, Daisuke Kurimoto (doctoral graduate), and Professor Jun Sato from the Graduate School of Bio-Information Media at Tokyo University of Technology (Hachioji City, Tokyo; President: Yutaka Kagawa) discovered that a fusion protein of human lactoferrin (hLF, Note 1) and human serum albumin (HSA), referred to as hLF-HSA, strongly inhibits cancer cell migration, which is closely related to cancer metastasis. This inhibition occurs by promoting the expression of Na+/H+ exchanger 7 (NHE7) (Note 3) in the Golgi apparatus (Note 2), leading to its alkalization, and by activating the caveolin-dependent endocytosis signal, an intracellular uptake signal. This finding is expected to lead to the development of new drug discovery strategies. The results of this research were published in the international scientific journal "FEBS Open Bio" of the Federation of European Biochemical Societies (FEBS) on March 24, 2026.
Development of biopharmaceuticals using hLF is underway at S&K BioPharma Co., Ltd. (Note 4), a biotech venture company.
**[Research Background]**
Cancer metastasis is a major clinical challenge affecting patient prognosis, and cancer cell migration is a crucial step in metastasis. Matrix metalloproteinase 1 (MMP1) is an enzyme that degrades the extracellular matrix and plays an important role in cancer cell migration. Previous research by the same group reported that hLF-HSA treatment reduced MMP1 expression in human lung adenocarcinoma cell line PC-14, thereby inhibiting migration (Reference 1). This study revealed that the decrease in MMP1 expression by hLF-HSA treatment is due to the disruption of Golgi pH homeostasis (functional inhibition) mediated by the promotion of NHE7 expression in the intracellular organelle (Golgi apparatus), and the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA.
**[Social and Academic Significance]**
The Golgi apparatus plays an extremely important role in cell migration, so its dysfunction due to the disruption of Golgi pH homeostasis is expected to be effective in inhibiting cancer cell migration. In this study, hLF-HSA disrupted Golgi pH homeostasis by promoting the expression of NHE7 in the Golgi apparatus, causing its functional inhibition. This functional inhibition reduced the expression of MMP1, which plays an important role in cancer cell migration, and inhibited migration. Furthermore, it was revealed that the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA leads to a decrease in MMP1 expression independently of its effect on NHE7. Through these two mechanisms, hLF-HSA strongly inhibits cancer cell migration.
Considering the function of the Golgi apparatus in normal cells, hLF-HSA might potentially cause side effects in normal cells. However, it has been clarified that hLF-HSA selectively inhibits the proliferation of cancer cells, while not affecting the proliferation of normal cells (Reference 2). Therefore, this research on hLF-HSA is noteworthy as a study demonstrating the effectiveness of a drug development concept for cancer cell migration inhibitors whose main action is Golgi functional inhibition.
Development of biopharmaceuticals using hLF is underway at S&K BioPharma Co., Ltd. (Note 4), a biotech venture company.
**[Research Background]**
Cancer metastasis is a major clinical challenge affecting patient prognosis, and cancer cell migration is a crucial step in metastasis. Matrix metalloproteinase 1 (MMP1) is an enzyme that degrades the extracellular matrix and plays an important role in cancer cell migration. Previous research by the same group reported that hLF-HSA treatment reduced MMP1 expression in human lung adenocarcinoma cell line PC-14, thereby inhibiting migration (Reference 1). This study revealed that the decrease in MMP1 expression by hLF-HSA treatment is due to the disruption of Golgi pH homeostasis (functional inhibition) mediated by the promotion of NHE7 expression in the intracellular organelle (Golgi apparatus), and the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA.
**[Social and Academic Significance]**
The Golgi apparatus plays an extremely important role in cell migration, so its dysfunction due to the disruption of Golgi pH homeostasis is expected to be effective in inhibiting cancer cell migration. In this study, hLF-HSA disrupted Golgi pH homeostasis by promoting the expression of NHE7 in the Golgi apparatus, causing its functional inhibition. This functional inhibition reduced the expression of MMP1, which plays an important role in cancer cell migration, and inhibited migration. Furthermore, it was revealed that the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA leads to a decrease in MMP1 expression independently of its effect on NHE7. Through these two mechanisms, hLF-HSA strongly inhibits cancer cell migration.
Considering the function of the Golgi apparatus in normal cells, hLF-HSA might potentially cause side effects in normal cells. However, it has been clarified that hLF-HSA selectively inhibits the proliferation of cancer cells, while not affecting the proliferation of normal cells (Reference 2). Therefore, this research on hLF-HSA is noteworthy as a study demonstrating the effectiveness of a drug development concept for cancer cell migration inhibitors whose main action is Golgi functional inhibition.