Human Lactoferrin/Human Serum Albumin Fusion Protein Potently Inhibits Cancer Metastasis-Related Cell Migration by Disrupting Cancer Cell Golgi Body pH Homeostasis
Mechanism of cancer cell migration inhibition by hLF-HSA fusion protein elucidated.
📋 Article Processing Timeline
- 📰 Published: March 30, 2026 at 19:30
- 🔍 Collected: March 30, 2026 at 22:56 (3h 26m after Published)
- 🤖 AI Analyzed: April 16, 2026 at 07:44 (392h 48m after Collected)
A research group led by Hana Nopia (Doctoral student), Assistant Professor Masahiro Kimura, Daisuke Kurimoto (Completed Doctoral Program), and Professor Jun Sato from the Graduate School of Bio-Media and Technology at Tokyo University of Technology (Hachioji City, Tokyo; President: Yutaka Kagawa) has discovered that a fusion protein of human lactoferrin (hLF, Note 1) and human serum albumin (HSA), termed hLF-HSA, potently inhibits migration (cell movement), which is closely related to cancer cell metastasis. This inhibition is achieved by promoting the expression of Na+/H+ exchanger 7 (NHE7, Note 3) expressed in the Golgi body (Note 2), leading to its alkalinization and activating caveolin-dependent endocytosis signals, which are intracellular uptake signals. This finding is expected to lead to the development of new drug discovery strategies. The research results were published in the international scientific journal 'FEBS Open Bio' by 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 challenge that affects patient prognosis, and cancer cell migration (cell movement) 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 reduces MMP1 expression in the human lung adenocarcinoma cell line PC-14, thereby inhibiting migration (Reference 1). This study revealed that the reduction in MMP1 expression by hLF-HSA treatment is due to the disruption of Golgi body pH homeostasis (functional impairment) mediated by the promotion of NHE7 expression, which is expressed in the intracellular organelle (Golgi body), and by caveolin-dependent endocytosis signals activated during the intracellular uptake of hLF-HSA.
【Social and Academic Significance】
The Golgi body plays an extremely important role in cell migration, and 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 body pH homeostasis and caused its functional impairment by promoting the expression of NHE7, which is expressed in the Golgi body. This functional impairment reduced the expression of MMP1, which plays a crucial role in cancer cell migration, and inhibited migration. Furthermore, it was revealed that caveolin-dependent endocytosis signals, activated during the intracellular uptake of hLF-HSA, lead 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 body in normal cells, hLF-HSA may potentially cause side effects in normal cells. However, it has been clarified that hLF-HSA selectively inhibits the proliferation of cancer cells while having no effect on the proliferation of normal cells (Reference 2). Therefore, the hLF-HSA in this study is noteworthy as an example demonstrating the effectiveness of a drug development concept targeting Golgi body functional impairment for inhibiting cancer cell migration.
【Publication Information】
Paper Title: Suppression of lung adenocarcinoma migration through organelle alkalization by human lactoferrin – albumin fusion
Authors: Hana Nopia, Masahiro Kimura, Daisuke Kurimoto &
FAQ
What is the main finding of this research?
The research found that a fusion protein called hLF-HSA can strongly inhibit cancer cell migration, a key step in metastasis, by disrupting the pH balance within the cancer cells' Golgi bodies.
How does hLF-HSA inhibit cancer cell migration?
hLF-HSA works through two main mechanisms: 1. It promotes the expression of NHE7 in the Golgi body, leading to its alkalinization and functional impairment, which reduces MMP1 expression. 2. It activates caveolin-dependent endocytosis signals during its uptake into the cell, which also leads to a reduction in MMP1 expression, independently of the Golgi body effect.
What is the significance of targeting the Golgi body's pH homeostasis?
The Golgi body is crucial for cell migration. Disrupting its pH homeostasis and impairing its function is a novel strategy to inhibit cancer cell migration. This research demonstrates the effectiveness of this approach.
Does hLF-HSA affect normal cells?
While the Golgi body is important in normal cells, studies have shown that hLF-HSA selectively inhibits cancer cell proliferation without affecting normal cell proliferation, suggesting a potential for targeted cancer therapy with fewer side effects.
What is the potential application of this research?
This research is expected to lead to the development of new drug discovery strategies for cancer metastasis, potentially leading to novel therapeutic agents that target the Golgi body's function.
Where was this research published?
The research was published in the international scientific journal 'FEBS Open Bio' by the Federation of European Biochemical Societies (FEBS).
Is hLF-HSA already available as a drug?
The development of biopharmaceuticals using hLF is being advanced by the bio-venture company S&K Biopharma Co., Ltd., but it is not yet available as a drug. This research provides a basis for further development.
What is MMP1 and why is its reduction important?
MMP1 (Matrix metalloproteinase 1) is an enzyme that breaks down the extracellular matrix. Reducing MMP1 expression is important because it hinders cancer cells' ability to migrate and invade surrounding tissues, thus inhibiting metastasis.
What is NHE7?
NHE7 (Na+/H+ exchanger 7) is a transporter protein expressed in the Golgi body that plays a role in maintaining its pH balance. The research found that hLF-HSA promotes the expression of NHE7.
What is caveolin-dependent endocytosis?
It is a process by which cells internalize substances from outside the cell, involving a protein called caveolin. This mechanism was found to be activated during the uptake of hLF-HSA and contributes to the inhibition of cancer cell migration.