Human Lactoferrin/Human Serum Albumin Fusion Protein Potently Inhibits Cancer Cell Migration Related to Metastasis by Disrupting Golgi pH Homeostasis
A research group at Tokyo University of Technology has discovered that a fusion protein of human lactoferrin and human serum albumin (hLF-HSA) inhibits cancer cell migration by disrupting Golgi apparatus pH homeostasis and activating caveolin-dependent endocytosis. This dual mechanism reduces the expression of MMP1, a key enzyme in cancer metastasis, offering a promising new strategy for drug development.
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- 📰 Published: March 30, 2026 at 19:30
- 🔍 Collected: March 30, 2026 at 22:56 (3h 26m after Published)
A research group at the Tokyo University of Technology (Hachioji, Tokyo; President: Yutaka Kagawa), including doctoral student Hana Nopia, Assistant Professor Masahiro Kimura, doctoral graduate Daisuke Kurimoto, and Professor Atsushi Sato of the Graduate School of Bioscience and Media, has discovered that a fusion protein of human lactoferrin (hLF, Note 1) and human serum albumin (HSA) (hLF-HSA) potently inhibits cell migration (cell movement), which is closely related to cancer metastasis. This is achieved through the promotion of Na+/H+ exchanger 7 (NHE7, Note 3) expression in the Golgi apparatus (Note 2), leading to its alkalization, and by triggering caveolin-dependent endocytosis, which serves as 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.
The development of biopharmaceuticals using hLF is being advanced by the bio-venture company S&K Biopharma Co., Ltd. (Note 4).
[Research Background]
Cancer metastasis is a critical clinical issue that determines a patient's prognosis, and cancer cell migration is a key step in this process. 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 reduces MMP1 expression in the human lung adenocarcinoma cell line PC-14, thereby suppressing migration (Reference 1). In this study, it was revealed that the reduction of MMP1 expression by hLF-HSA treatment is caused by the disruption of Golgi pH homeostasis (functional inhibition) via the promotion of NHE7 expression in the organelle (Golgi apparatus), as well as by the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA.
[Social and Academic Significance]
Because the Golgi apparatus plays an extremely important role in cell migration, its dysfunction due to the disruption of pH homeostasis is expected to be effective in inhibiting cancer cell migration. In this study, hLF-HSA disrupted Golgi pH homeostasis and caused functional inhibition by promoting the expression of NHE7 in the Golgi. This functional inhibition reduced the expression of MMP1, which plays a key role in cancer cell migration, thereby inhibiting migration. Furthermore, it was revealed that the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA leads to a reduction in MMP1 expression independently of the aforementioned effect on NHE7. Through these two mechanisms, hLF-HSA potently inhibits cancer cell migration.
Considering the function of the Golgi apparatus in normal cells, there is a possibility that hLF-HSA could cause side effects in normal cells. However, it has been shown that while hLF-HSA selectively causes growth inhibition in cancer cells, it does not affect the growth of normal cells (Reference 2). Therefore, the hLF-HSA used in this study is noteworthy as a research example demonstrating the effectiveness of a drug development concept that targets the inhibition of Golgi function as the primary mechanism for inhibiting cancer cell migration.
[Paper Information]
Paper Title: Suppression of lung adenocarcinoma migration through organelle alkalization by human lactoferrin – albumin fusion
Authors: Hana Nopia, Masahiro Kimura, Daisuke Kurimoto & Atsushi Sato
Journal: FEBS Open Bio
Publication Date: March 24, 2026
https://doi.org/10.1002/2211-5463.70237
[Glossary]
(Note 1) hLF: A protein that functions in innate immunity and possesses many physiological activities, including anti-tumor, anti-inflammatory, antioxidant, and nerve regeneration effects.
(Note 2) Golgi apparatus: An organelle that modifies, sorts, and transports proteins and lipids sent from the endoplasmic reticulum to destinations inside and outside the cell. It is involved in the regulation of cell migration.
(Note 3) NHE7: In lung adenocarcinoma cells, it maintains the weak acidity (pH homeostasis) of intracellular organelles (Golgi apparatus) by releasing H+ from them.
(Note 4) S&K Biopharma Co., Ltd. (Headquarters: Kawasaki, Kanagawa; Representative: Shinji Kagaya): Develops therapeutic drugs for spinal cord injury, sepsis, rapidly progressive glomerulonephritis, cancer, etc., using human lactoferrin. https://skagayasandk.wixsite.com/website
[References]
(Reference 1) Hana Nopia et al., "Albumin fusion with human lactoferrin shows enhanced inhibition of cancer cell migration," Biometals (2023)
(Reference 2) Ueda et al., "Albumin fusion at the N-terminus or C-terminus of human lactoferrin leads to improved pharmacokinetics and anti-proliferative effects on cancer cell lines," Eur J Pharm Sci. (2020)
■ Tokyo University of Technology, Graduate School of Bioscience and Media, Atsushi Sato & Masahiro Kimura (Biological Drug Discovery) Laboratory
Conducts research on biological drug discovery based on genetic recombination, biochemistry, and cell culture technology. In particular, the lab promotes functional analysis of lactoferrin, a protein that functions in innate immunity, its development as a biopharmaceutical, and the creation of peptides that mimic lactoferrin activity.
[Main Research Themes]
1. Functional analysis of lactoferrin functioning in innate immunity (especially anti-tumor and nerve regeneration effects)
2. Development of novel lactoferrin formulations with enhanced in vivo stability and their application as biopharmaceuticals
3. Development of biopharmaceuticals targeting disease-related glycans
4. Creation of lactoferrin-mimetic peptides
[Laboratory Website URL] https://www.teu.ac.jp/info/lab/project/bio/dep.html?id=5
The development of biopharmaceuticals using hLF is being advanced by the bio-venture company S&K Biopharma Co., Ltd. (Note 4).
[Research Background]
Cancer metastasis is a critical clinical issue that determines a patient's prognosis, and cancer cell migration is a key step in this process. 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 reduces MMP1 expression in the human lung adenocarcinoma cell line PC-14, thereby suppressing migration (Reference 1). In this study, it was revealed that the reduction of MMP1 expression by hLF-HSA treatment is caused by the disruption of Golgi pH homeostasis (functional inhibition) via the promotion of NHE7 expression in the organelle (Golgi apparatus), as well as by the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA.
[Social and Academic Significance]
Because the Golgi apparatus plays an extremely important role in cell migration, its dysfunction due to the disruption of pH homeostasis is expected to be effective in inhibiting cancer cell migration. In this study, hLF-HSA disrupted Golgi pH homeostasis and caused functional inhibition by promoting the expression of NHE7 in the Golgi. This functional inhibition reduced the expression of MMP1, which plays a key role in cancer cell migration, thereby inhibiting migration. Furthermore, it was revealed that the caveolin-dependent endocytosis signal activated during the intracellular uptake of hLF-HSA leads to a reduction in MMP1 expression independently of the aforementioned effect on NHE7. Through these two mechanisms, hLF-HSA potently inhibits cancer cell migration.
Considering the function of the Golgi apparatus in normal cells, there is a possibility that hLF-HSA could cause side effects in normal cells. However, it has been shown that while hLF-HSA selectively causes growth inhibition in cancer cells, it does not affect the growth of normal cells (Reference 2). Therefore, the hLF-HSA used in this study is noteworthy as a research example demonstrating the effectiveness of a drug development concept that targets the inhibition of Golgi function as the primary mechanism for inhibiting cancer cell migration.
[Paper Information]
Paper Title: Suppression of lung adenocarcinoma migration through organelle alkalization by human lactoferrin – albumin fusion
Authors: Hana Nopia, Masahiro Kimura, Daisuke Kurimoto & Atsushi Sato
Journal: FEBS Open Bio
Publication Date: March 24, 2026
https://doi.org/10.1002/2211-5463.70237
[Glossary]
(Note 1) hLF: A protein that functions in innate immunity and possesses many physiological activities, including anti-tumor, anti-inflammatory, antioxidant, and nerve regeneration effects.
(Note 2) Golgi apparatus: An organelle that modifies, sorts, and transports proteins and lipids sent from the endoplasmic reticulum to destinations inside and outside the cell. It is involved in the regulation of cell migration.
(Note 3) NHE7: In lung adenocarcinoma cells, it maintains the weak acidity (pH homeostasis) of intracellular organelles (Golgi apparatus) by releasing H+ from them.
(Note 4) S&K Biopharma Co., Ltd. (Headquarters: Kawasaki, Kanagawa; Representative: Shinji Kagaya): Develops therapeutic drugs for spinal cord injury, sepsis, rapidly progressive glomerulonephritis, cancer, etc., using human lactoferrin. https://skagayasandk.wixsite.com/website
[References]
(Reference 1) Hana Nopia et al., "Albumin fusion with human lactoferrin shows enhanced inhibition of cancer cell migration," Biometals (2023)
(Reference 2) Ueda et al., "Albumin fusion at the N-terminus or C-terminus of human lactoferrin leads to improved pharmacokinetics and anti-proliferative effects on cancer cell lines," Eur J Pharm Sci. (2020)
■ Tokyo University of Technology, Graduate School of Bioscience and Media, Atsushi Sato & Masahiro Kimura (Biological Drug Discovery) Laboratory
Conducts research on biological drug discovery based on genetic recombination, biochemistry, and cell culture technology. In particular, the lab promotes functional analysis of lactoferrin, a protein that functions in innate immunity, its development as a biopharmaceutical, and the creation of peptides that mimic lactoferrin activity.
[Main Research Themes]
1. Functional analysis of lactoferrin functioning in innate immunity (especially anti-tumor and nerve regeneration effects)
2. Development of novel lactoferrin formulations with enhanced in vivo stability and their application as biopharmaceuticals
3. Development of biopharmaceuticals targeting disease-related glycans
4. Creation of lactoferrin-mimetic peptides
[Laboratory Website URL] https://www.teu.ac.jp/info/lab/project/bio/dep.html?id=5