ArticleCancer science2021
Suppression of lysosomal acid alpha-glucosidase impacts the modulation of transcription factor EB translocation in pancreatic cancer.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Review
- Article
- Multi-omics analysis identifies GAA as an independent poor prognostic biomarker and candidate therapeutic target in angioimmunoblastic T-cell lymphoma.Frontiers in immunology · 2026Article
- Pan-cancer analysis and oncogenic implications ofJournal of cell communication and signaling · 2025Article
- Synthesis and multi-target antiproliferative evaluation of novel 1,2,4-triazole-3-thione analogues against breast cancer:RSC advances · 2025Article
- Expression of ZKSCAN3 protein suppresses proliferation, migration, and invasion of pancreatic cancer through autophagy.Cancer science · 2024Article
- Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives.Molecular cancer · 2024Review
- Lysosomal glucose sensing and glycophagy in metabolism.Trends in endocrinology and metabolism: TEM · 2023Review
- Identification and validation of the reference genes in the echiuran worm Urechis unicinctus based on transcriptome data.BMC genomics · 2023Article
- Gemcitabine promotes autophagy and lysosomal function through ERK- and TFEB-dependent mechanisms.Cell death discovery · 2023Article
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates.Frontiers in oncology · 2022Article
- Autophagy and the Lysosomal System in Cancer.Cells · 2021Review
- Suppression of lysosomal acid alpha-glucosidase impacts the modulation of transcription factor EB translocation in pancreatic cancer.Cancer science · 2021Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Lysosomal degradation plays a crucial role in the metabolism of biological macromolecules supplied by autophagy. The regulation of the autophagy-lysosome system, which contributes to intracellular homeostasis, chemoresistance, and tumor progression, has recently been revealed as a promising therapeutic approach for pancreatic cancer (PC). However, the details of lysosomal catabolic function in PC cells have not been fully elucidated. In this study, we show evidence that suppression of acid alpha-glucosidase (GAA), one of the lysosomal enzymes, improves chemosensitivity and exerts apoptotic effects on PC cells through the disturbance of expression of the transcription factor EB. The levels of lysosomal enzyme were elevated by gemcitabine in PC cells. In particular, the levels of GAA were responsive to gemcitabine in a dose-dependent and time-dependent manner. Small interfering RNA against the GAA gene (siGAA) suppressed cell proliferation and promoted apoptosis in gemcitabine-treated PC cells. In untreated PC cells, we observed accumulation of depolarized mitochondria. Gene therapy using adenoviral vectors carrying shRNA against the GAA gene increased the number of apoptotic cells and decreased the tumor growth in xenograft model mice. These results indicate that GAA is one of the key targets to improve the efficacy of gemcitabine and develop novel therapies for PC.
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