Abstract
DTX3L (Deltex E3 ubiquitin ligase 3 L) is an E3 ubiquitin ligase, a member of the deltex family. It is also known as B-lymphoma and BAL-associated protein (BBAP). DTX3L has been proven to play an important role in various tumor development; however, its role in pancreatic cancer remains unknown. So, we analyzed the DTX3L expression in pancreatic cancer based on the TCGA database and verified it in our samples by qRT‑PCR and western blot. We identified that DTX3L was highly expressed in pancreatic cancer, and its expression level was significantly negatively correlated with patients’ survival. Using CCK8, colony formation, transwell, and wound healing assays, we found that upregulated DTX3L promotes pancreatic cancer cell proliferation, invasion, and migration. Mechanically, DTX3L combined with EGFR (epidermal growth factor receptor) and prevented the ubiquitination degradation of it. Upregulated EGFR activated the FAK/PI3K/Akt pathway and promoted the progression of pancreatic cancer. Moreover, we found that DTX3L can weaken pancreatic cancer cells’ sensitivity to chemotherapy using the orthotopic implant tumor model. In conclusion, DTX3L accelerates pancreatic cancer progression by EGFR dependent FAK/PI3K/Akt pathway activation and may become a potential target for pancreatic cancer treatment.
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Data Availability
All data involved in this study are available from the corresponding authors upon reasonable request.
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Funding
This study was supported by the National Natural Science Foundation of China (31971518) the National Key Research and Development Program of China (2020YFA0713804) and Youth Scientific Research Project of Nantong Commission of Health (QNZ2022016).
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Study concept and design: Liang Chen, Hong Zang, Yudong Qiu. Experiments, experimental data analysis: Liang Chen, Wenyang Niu, Yudong Qiu. Statistical analysis: Liang Chen, Wenyang Niu. Drafting of manuscript: Liang Chen, Hong Zang, Yudong Qiu.
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Chen, L., Niu, W., Zang, H. et al. DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis. Biochem Genet 62, 814–830 (2024). https://doi.org/10.1007/s10528-023-10451-4
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DOI: https://doi.org/10.1007/s10528-023-10451-4