Metabolism remodeling in pancreatic ductal adenocarcinoma

Authors:

Jin-Tao Li1, Yi-Ping Wang1, Miao Yin1 and Qun-Ying Lei1, 2
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Affiliations:

1 Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China.

2 Lead Contact.

Keywords: 

PDAC, KRAS, metabolism, tumor microenvironment.

Abbreviatons:

5-HT – 5-hydroxytryptamine,

αKG – alpha-ketoglutarate,

ADM – acinar-to-ductal metaplasia,

Asp – aspartate,

ACLY – ATP-citrate lyase,

ECM – extracellular matrix,

GAPDH – glyceraldehyde-3-phosphate dehydrogenase,

Gln – glutamine,

HBP – hexosamine biosynthetic pathway,

HIF – hypoxia-inducible factor,

LDH – lactate dehydrogenase,

LDLR – low density lipoprotein receptor,

PanIN – pancreatic intraepithelial neoplasia,

PDAC – pancreatic ductal adenocarcinoma,

PPP – pentose phosphate pathway,

PSC – pancreatic stellate cell,

R5P – ribose-5-phosphate,

ROS – reactive oxygen species,

TAM – tumor-associated macrophage,

TCA – tricarboxylic acid cycle.

Corresponding Author(s):

Miao Yin, Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Repub-lic of China; miaoyin@fudan.edu.cn Qun-Ying Lei, Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Repub-lic of China; qlei@fudan.edu.cn

Conflict of interest statement:

The authors have declared that no conflict of interest ex-ists.

Please cite this article as:

Jin-Tao Li, Yi-Ping Wang, Miao Yin and Qun-Ying Lei (2019). Metabolism remodeling in pancreatic ductal adenocarcinoma. Cell Stress 3(12): 316-368. doi: 10.15698/cst2019.12.205

© 2019 Li et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of death of patients with malignant cancers by 2030. Current options of PDAC treatment are limited and the five-year survival rate is less than 8%, leading to an urgent need to explore innovatively therapeutic strategies. PDAC cells exhibit extensively reprogrammed metabolism to meet their energetic and biomass demands under extremely harsh conditions. The metabolic changes are closely linked to signaling triggered by activation of oncogenes like KRAS as well as inactivation of tumor suppressors. Furthermore, tumor microenvironmental factors including extensive desmoplastic stroma reaction result in series of metabolism remodeling to facilitate PDAC development. In this review, we focus on the dysregulation of metabolism in PDAC and its surrounding microenvironment to explore potential metabolic targets in PDAC therapy.