2. Academic Validation
  3. UDP-glucose dehydrogenase supports autophagy-deficient PDAC growth via increasing hyaluronic acid biosynthesis

UDP-glucose dehydrogenase supports autophagy-deficient PDAC growth via increasing hyaluronic acid biosynthesis

  • Cell Rep. 2024 Feb 16;43(2):113808. doi: 10.1016/j.celrep.2024.113808.
Minghe Fan 1,  Sihan Huo 1,  Yuyao Guo 1,  Ruoxuan Wang 1,  Wenqin Hao 1,  Ziyang Zhang 1,  Lina Wang 1,  Ying Zhao 2
Affiliations

Affiliations

  • 1 Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, State Key Laboratory of Molecular Oncology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University International Cancer Institute, Peking University Health Science Center, Beijing 100191, China.
  • 2 Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, State Key Laboratory of Molecular Oncology, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Peking University International Cancer Institute, Peking University Health Science Center, Beijing 100191, China; Peking University Cancer Hospital and Institute, Beijing 100142, China. Electronic address: [email protected].
PMID: 38367236 DOI: 10.1016/j.celrep.2024.113808
Abstract

Autophagy is an essential degradation and recycling process that maintains cellular homeostasis during stress or nutrient deprivation. However, certain types of tumors such as pancreatic cancers can circumvent Autophagy inhibition to sustain growth. The mechanism that autophagy-deficient pancreatic ductal adenocarcinoma (PDAC) uses to grow under nutrient deprivation is poorly understood. Our data show that nutrient deprivation in PDAC results in UDP-glucose dehydrogenase (UGDH) degradation, which is dependent on autophagic cargo receptor sequestosome 1 (p62). Moreover, we demonstrate that accumulated UGDH is indispensable for autophagy-deficient PDAC cells proliferation by promoting hyaluronic acid (HA) synthesis upon energy deprivation. Using an orthotopic mouse model of PDAC, we find that inhibition of HA synthesis by targeting UGDH in PDAC reduces tumor weight. Thus, the combined inhibition of HA and Autophagy might be an attractive strategy for PDAC treatment.

Keywords

CP: Cancer; CP: Metabolism; HA; PDAC; UDP-glucose dehydrogenase; UGDH; autophagy; hyaluronic acid; p62; pancreatic ductal adenocarcinoma; sequestosome 1.

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