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

Published:27 February 2024 DOI: 10.1016/j.celrep.2024.113808 PMID: 38367236
Minghe Fan,?Sihan Huo,?Yuyao Guo,?Ruoxuan Wang,?Wenqin Hao,?Ziyang Zhang,?Lina Wang,?Ying Zhao

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.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
Hygromycin B 31282-04-9 C20H37N3O13 576 suppliers $35.00-$1480.00
Hygromycin B 31282-04-9 C20H37N3O13 576 suppliers $35.00-$1480.00
Hygromycin B 31282-04-9 C20H37N3O13 576 suppliers $35.00-$1480.00
Hygromycin B 31282-04-9 C20H37N3O13 576 suppliers $35.00-$1480.00
PUROMYCIN 53-79-2 C22H29N7O5 146 suppliers $39.00-$1200.00
PUROMYCIN 53-79-2 C22H29N7O5 146 suppliers $39.00-$1200.00
PUROMYCIN 53-79-2 C22H29N7O5 146 suppliers $39.00-$1200.00
PUROMYCIN 53-79-2 C22H29N7O5 146 suppliers $39.00-$1200.00
HyGromycin B 31282-04-9 C20H37N3O13 - Inquiry
HyGromycin B 31282-04-9 C20H37N3O13 - Inquiry

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