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European Archives of Oto-Rhino-Laryngology

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Open Access 16-11-2022 | Leukoplakia | Laryngology

Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia

Authors: Haitong Li, Shasha Zhang, Shuihong Zhou, Yangyang Bao, Xiaojuan Cao, Lifang Shen, Bin Xu, Weimin Gao, Yunzhen Luo

Published in: European Archives of Oto-Rhino-Laryngology | Issue 4/2023

Abstract

Purpose

The mechanism underlying malignant transformation of vocal fold leukoplakia (VFL) and the precise role of the expression of pepsin in VFL remain unclear. This study aimed to investigate the effects of acidified pepsin on VFL epithelial cell growth and migration, and also identify pertinent molecular mechanisms.

Methods

Immunochemistry and Western blotting were performed to measure glucose transporter type 1 (GLUT1), monocarboxylate transporters 4 (MCT4), and Hexokinase-II (HK-II) expressions. Cell viability, cell cycle, apoptosis, and migration were investigated by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. Glycolysis-related contents were determined using the corresponding kits. Mitochondrial HK-II was photographed under a confocal microscope using Mito-Tracker Red.

Results

It was found: the expression of pepsin and proportion of pepsin+ cells in VFL increased with the increased dysplasia grade; acidified pepsin enhanced cell growth and migration capabilities of VFL epithelial cells, reduced mitochondrial respiratory chain complex I activity and oxidative phosphorylation, and enhanced aerobic glycolysis and GLUT1 expression in VFL epithelial cells; along with the transfection of GLUT1 overexpression plasmid, 18FFDG uptake, lactate secretion and growth and migration capabilities of VFL epithelial cell were increased; this effect was partially blocked by the glycolysis inhibitor 2-deoxy-glucose; acidified pepsin increased the expression of HK-II and enhanced its distribution in mitochondria of VFL epithelial cells.

Conclusion

It was concluded that acidified pepsin enhances VFL epithelial cell growth and migration abilities by reducing mitochondrial respiratory complex I activity and promoting metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis.

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Title: Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia
Authors: Haitong Li
Shasha Zhang
Shuihong Zhou
Yangyang Bao
Xiaojuan Cao
Lifang Shen
Bin Xu
Weimin Gao
Yunzhen Luo
Publication date: 16-11-2022
Publisher: Springer Berlin Heidelberg
Keywords: Leukoplakia
Laryngeal Cancer
Laryngeal Cancer
Leukoplakia
Published in: European Archives of Oto-Rhino-Laryngology / Issue 4/2023
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-022-07729-5

2024 ASCO Annual Meeting

Springer Medicine

Pepsin enhances glycolysis to promote malignant transformation of vocal fold leukoplakia epithelial cells with dysplasia

Abstract

Purpose

Methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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