VPS45 promotes the progression of hepatocellular carcinoma by recycling β1 integrin to the cell membrane via the endocytic pathway
- 20.06.2025
- Original Article―Liver, Pancreas, and Biliary Tract
Erschienen in:
- Verfasst von
- Takashi Ofuchi
- Hajime Otsu
- Kiyotaka Hosoda
- Tomohiko Ikehara
- Akinori Tsujimoto
- Satoshi Higuchi
- Shohei Shibuta
- Yuya Ono
- Kosuke Hirose
- Yasuo Tsuda
- Yusuke Yonemura
- Takaaki Masuda
- Hiromitsu Hayashi
- Masaaki Iwatsuki
- Koshi Mimori
- Erschienen in
- Journal of Gastroenterology | Ausgabe 9/2025
Abstract
Background
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis, which is often driven by chromosomal amplifications at 1q. Vacuolar sorting protein 45 (VPS45), a gene located on chromosome 1q, is involved in the endocytic recycling pathway; however, its role in HCC remains unclear. In this study, we aimed to investigate the functional significance of VPS45 in the progression of HCC.
Methods
VPS45 expression was analyzed using public databases, clinical HCC samples, and cell lines. Functional assays, including VPS45 knockout and rescue experiments, were conducted to assess the effect on tumor progression in vitro and in vivo. The molecular mechanisms underlying VPS45 function, particularly its role in β1 integrin recycling and FAK-AKT signaling activation, were also explored.
Results
VPS45 expression was significantly elevated in HCC owing to DNA copy number amplification and correlated with poor prognosis. Moreover, VPS45 knockout suppressed cell proliferation, migration, and invasion, while promoting apoptosis. VPS45 interacted with syntaxin16 and rabenosyn-5 to facilitate the recycling of β1 integrin to the cell membrane, thereby activating FAK-AKT signaling, which promotes oncogenic phenotypes. In xenograft models, VPS45 knockout significantly suppressed tumor growth, further supporting its role in HCC progression.
Conclusions
VPS45 is a key oncogene in HCC that promotes tumor progression by enhancing β1 integrin recycling and activating FAK-AKT signaling. Given its strong association with poor prognosis and tumor malignancy, VPS45 may serve as a promising prognostic biomarker and a potential therapeutic target for HCC.
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- Titel
- VPS45 promotes the progression of hepatocellular carcinoma by recycling β1 integrin to the cell membrane via the endocytic pathway
- Verfasst von
-
Takashi Ofuchi
Hajime Otsu
Kiyotaka Hosoda
Tomohiko Ikehara
Akinori Tsujimoto
Satoshi Higuchi
Shohei Shibuta
Yuya Ono
Kosuke Hirose
Yasuo Tsuda
Yusuke Yonemura
Takaaki Masuda
Hiromitsu Hayashi
Masaaki Iwatsuki
Koshi Mimori
- Publikationsdatum
- 20.06.2025
- Verlag
- Springer Nature Singapore
- Erschienen in
-
Journal of Gastroenterology / Ausgabe 9/2025
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922 - DOI
- https://doi.org/10.1007/s00535-025-02278-0
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