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journal article·2024-07Open access

Inhibition of DEF‐p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer

Sicong Huang, Jiaqi Yang, Teng Xie, Yangwei Jiang, Yifan Hong, Xinyuan Liu, Xuyan He, Damiano Buratto, Dong Zhang, Ruhong Zhou, Tingbo Liang, Xueli Bai

Advanced Science· Volume 11· Issue 28
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Abstract

Abstract The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti‐tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin‐proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF‐mimicking peptide, peptide‐031, designed to disrupt the DEF‐p65 interaction. The effectiveness of peptide‐031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide‐031 is a promising therapeutic agent with potent anti‐tumor effects.
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Research context

OpenAlex topics: Pancreatic and Hepatic Oncology Research · Neuroendocrine Tumor Research Advances · Cancer, Hypoxia, and Metabolism

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

Affiliations

Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310000 China

Key Laboratory of Pancreatic Disease of Zhejiang Province Hangzhou 310000 China

Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province Hangzhou 310000 China

Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases Hangzhou 310000 China

Institute of Quantitative Biology, College of Life Sciences Zhejiang University Hangzhou 310000 China

Shanghai Institute for Advanced Study Zhejiang University Shanghai 200000 China

Life Sciences Institute Zhejiang University Hangzhou 310000 China

Department of Chemistry Columbia University New York 10027 USA

Cancer Center Zhejiang University Hangzhou 310000 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Key Research and Development Program of Zhejiang Province · China Postdoctoral Science Foundation · Fundamental Research Funds for the Provincial Universities of Zhejiang · Natural Science Foundation of Zhejiang Province · Major Projects of Special Development Funds in Zhangjiang National Independent Innovation Demonstration Zone, Shanghai

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