The University of Toledo Translation Journal of Medical Sciences 
UTJMS 2023 May 5; 11(1):e1-e1 

https://dx.doi.org/10.46570/utjms.vol11-2023-733 

Haemtology and Oncology Abstract, Department of Medicine Research Symposium 

Probing Dynamics of 14-3-3: A Potential 
Remedy for Pancreatic Cancer 

Deepti Gurung1*, JoAnne J Babula1, Catherine JR Rajendran1, JingYuan Liu1 
1Division of Haematology and Oncology, Department of Medicine, The University 
of Toledo, Toledo, OH 43614 

*Corresponding author: Deepti.gurung@utoledo.edu

Published: 05 May 2023 

Introduction: Pancreatic cancer is the third-most-common cause of cancer-related deaths in the U.S. 
Drug development for pancreatic cancer has greatly advanced over the past decade. However, 
chemoresistance exacerbates challenges in improving the efficacy of the current treatment regimens. 14-
3-3 is a small, homo-dimeric, regulatory protein, mostly expressed in epithelial cells. It promotes cancer
metastasis, confers resistance to anticancer drugs and radiation, and increases cell cycle arrest upon
DNA damage. Overexpression of 14-3-3 is correlated with a poor survival rate among pancreatic cancer
patients. 14-3-3, therefore, is a potential anticancer target for the treatment of pancreatic cancer. It
belongs to the 14-3-3-protein family with other six isoforms involved in diverse cellular pathways. The
discovery and development of 14-3-3-isoform-selective inhibitors are indispensable because of the pan-
inhibitory nature of currently available inhibitors of 14-3-3 isoforms.

Methods: Molecular Dynamics Simulation and Biological Small-angle X-ray scattering were used to 
study protein dynamics of 14-3-3- isoforms.   

Results: We found potential differences in conformational states between 14-3-3-isoforms when 
unbound by a ligand and similarities in bound states. Unbound 14-3-3 displayed unique, wide-open 
conformation i.e. significant flexibility, in comparison to other unbound isoforms. Principal Component 
Analysis captured a highly, flexible loop region between Helices 3 and 4 which could play an important 
role in regulating the open-close conformational change in 14-3-3-isoforms.    

Conclusion: Our study revealed that the dynamics are not conserved among 14-3-3 isoforms and this 
promising finding could lead to the development and discovery of 14-3-3-isoform-selective inhibitors 
for pancreatic cancer. 

https://dx.doi.org/10.46570/utjms.vol11-2023-733
mailto:Deepti.gurung@utoledo.edu