DataVXAdvanced SciencePaper
journal article·2025-11Open access

SP1‐Mediated Glycolytic Reprogramming Promotes Tumorigenesis and Progression in Pancreatic Cancer

Hexing Hang, Mengyu Yu, Linxi Zhu, Neng Tang, Xiao Fu, Zhenghua Cai, Minghao Yan, Yi Chen, Lei Yang, Jianzhuang Wu, Jiatong Tang, Yu Xie, Qi Li, Xu Fu, Liang Mao, Jun Chen, Fanqing Meng, Bo Kong, Xiaodong Han, Chao Yan, Yudong Qiu, Hao Cheng

Advanced Science· Volume 12· Issue 42
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Source abstract

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, commonly progressing from pancreatic intraepithelial neoplasia (PanIN). However, the molecular alterations in PanIN lesions and their contribution to PDAC progression remain poorly defined. Here, using laser capture microdissection‐based proteomics of patient tissues, early metabolic remodeling and upregulation of the transcriptional factor specificity protein 1 (SP1) in PanIN lesions are identified, which persisted into the PDAC stage. That SP1 overexpression promoted PDAC proliferation is demonstrated in patient‐derived organoid xenograft models (PDOXs), while deletion of Sp1 inhibited tumorigenesis and progression in a transgenic mouse model of PDAC ( Kras LSL‐G12D/+ ; Trp53 LSL‐R172H/+ ; Sp1 LOXP/LOXP ; Pdx1‐Cre ). ChIP‐seq and isotope tracing revealed that SP1 enhances aerobic glycolysis by transcriptionally activating 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase (PFKFB4), a key regulator of glycolysis. Combination therapy targeting SP1 and PFKFB4 demonstrated significant efficacy in PDAC models in vivo. The findings suggest that SP1 is a critical regulator of PDAC initiation and progression through its control of metabolic remodeling. Targeting SP1 and PFKFB4 represents a promising therapeutic strategy for PDAC treatment.
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Research context

OpenAlex topics: Pancreatic and Hepatic Oncology Research · Cancer, Hypoxia, and Metabolism · Epigenetics and DNA Methylation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pancreatic and Metabolic Surgery Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu 210008 China

Department of Pathology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu 210008 China

Jiangsu Key Laboratory of Molecular Medicine Medical School Nanjing University Nanjing Jiangsu 210093 China

The Affiliated Jiangning Hospital of Nanjing Medical University Nanjing Jiangsu 211100 China

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science Medical School Nanjing University Nanjing Jiangsu 210093 China

Clinical and Translational Research Center Affiliated Hospital of Nantong University & Department of Oncology Medical School of Nantong University Nantong Jiangsu 226007 China

State Key Laboratory of Pharmaceutical Biotechnology School of life Sciences Nanjing University Nanjing Jiangsu 210023 China

Department of General Visceral and Transplantation Surgery University of Heidelberg 69117 Heidelberg Germany

Chemistry and Biomedicine Innovation Center Institute of Artificial Intelligence Biomedicine Nanjing University Nanjing Jiangsu 210034 China

Institute of Pancreatology Nanjing University Nanjing Jiangsu 210008 China

Funding

National Natural Science Foundation of China · Ministry of Science and Technology of the People's Republic of China

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