Objectives: Transcriptional Repression of SP1 by FOXA3 Suppresses Pancreatic Cancer Cell Proliferation and Migration. Methods: Using overexpression and RNAi (RNAi) techniques, the expression levels of SP1 and FOXA3 in pancreatic cancer cells were adjusted, respectively. Cell proliferation and migration abilities were assessed by CCK - 8 proliferation assay and wound healing assay. The regulatory relationship between SP1 and FOXA3 expression was confirmed by Western blot analysis. Results: Functional assays showed that knockdown of SP1 significantly suppressed the proliferation and migration abilities of pancreatic cancer cells, indicating an oncogenic role of SP1 in pancreatic cancer. Mechanistic studies further demonstrated that overexpression of FOXA3 markedly downregulated the protein expression level of SP1. Conclusion: By transcriptionally suppressing SP1 expression, FOXA3 prevents the malignant progression of pancreatic cancer and attenuates SP1- mediated promotion of tumor cell proliferation and migration. Targeting the FOXA3/SP1 regulatory axis may offer a novel therapeutic approach for pancreatic cancer treatment.
Zhang C, Chen Y, Zhu S, et al., 2025, Targeting CLK1/SRSF7 Axis-Dependent Alternative Splicing Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy and Immunotherapy. Drug Resistance Updates, 83: 101292.
Wu Y, Lin B, Xie Z, et al., 2025, SUMOylation of RAD51 Upregulates GOLPH3 Expression and Promotes Cisplatin Resistance in Colon Cancer Cells by Sp1 Transcriptional Activity. Biochemical Pharmacology, 236: 116888.
Yang M, Li LJ, Qiu GP, et al., 2025, Specificity Protein 1 Initiates Epithelial-Mesenchymal Transition of Circulating Tumor Cells to Inhibit Metastasis in Prostate Cancer. Cancer Cell International, 25(1): 255.
Gu J, Zhang J, Xia R, et al., 2024, The Role of Histone H1.2 in Pancreatic Cancer Metastasis and Chemoresistance. Drug Resistance Updates, 73: 101027.
Lusby R, Demirdizen E, Inayatullah M, et al., 2025, Pan-Cancer Drivers of Metastasis. Molecular Cancer, 24(1): 2.
Donahue KL, Watkoske HR, Kadiyala P, et al., 2024, Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth. Cancer Discovery, 14(10): 1964–1989.
Liu Y, Song Y, Cao M, et al., 2022, A Novel EHD1/CD44/Hippo/SP1 Positive Feedback Loop Potentiates Stemness and Metastasis in Lung Adenocarcinoma. Clinical and Translational Medicine, 12(4): e836.
Zhu L, Lin S, Cui W, et al., 2022, A Nanomedicine Enables Synergistic Chemo/Photodynamic Therapy for Pancreatic Cancer Treatment. Biomaterials Science, 10(13): 3624–3636.
Ying H, Kimmelman AC, Bardeesy N, et al., 2025, Genetics and Biology of Pancreatic Ductal Adenocarcinoma. Genes & Development, 39(1–2): 36–63.
Romano R, Picca A, Eusebi LHU, et al., 2021, Extracellular Vesicles and Pancreatic Cancer: Insights on the Roles of miRNA, lncRNA, and Protein Cargos in Cancer Progression. Cells, 10(6): 1361.
Sha G, Zhang W, Jiang Z, et al., 2024, Exosomal Non-Coding RNA: A New Frontier in Diagnosing and Treating Pancreatic Cancer: A Review. International Journal of Biological Macromolecules, 263(Pt 1): 130149.
Li Q, Chao Q, Liu Y, et al., 2021, Deubiquitinase ZRANB1 Drives Hepatocellular Carcinoma Progression Through SP1-LOXL2 Axis. American Journal of Cancer Research, 11(10): 4807–4825.