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Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets
Published on: February 2, 2024
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SP1-Mediated Glycolytic Reprogramming Promotes Tumorigenesis and Progression in Pancreatic Cancer
Hexing Hang1,2,3, Mengyu Yu4, Linxi Zhu3
1Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210008, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 20, 2025
Summary
Specificity protein 1 (SP1) drives pancreatic cancer initiation and progression by altering metabolism. Targeting SP1 and PFKFB4 offers a promising therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Oncology
- Molecular Biology
- Metabolic Research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer often arising from pancreatic intraepithelial neoplasia (PanIN).
- Molecular changes in PanIN and their role in PDAC progression are not well understood.
Purpose of the Study:
- To investigate molecular alterations in early PanIN lesions.
- To define the role of specificity protein 1 (SP1) in PDAC initiation and progression.
- To explore SP1's mechanism in metabolic reprogramming and identify therapeutic targets.
Main Methods:
- Laser capture microdissection-based proteomics of patient tissues.
- Patient-derived organoid xenograft models (PDOXs) and transgenic mouse models.
- Chromatin immunoprecipitation sequencing (ChIP-seq) and isotope tracing.
Main Results:
- Early metabolic remodeling and SP1 upregulation were identified in PanIN lesions, persisting in PDAC.
- SP1 overexpression promoted PDAC proliferation; SP1 deletion inhibited tumorigenesis.
- SP1 was found to enhance aerobic glycolysis by activating PFKFB4.
Conclusions:
- SP1 is a critical regulator of PDAC initiation and progression via metabolic remodeling.
- Targeting SP1 and PFKFB4 demonstrates significant therapeutic potential for PDAC.
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