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15-06-2023 | Metastasis

Pancreatic cancer epigenetics: adaptive metabolism reprograms starving primary tumors for widespread metastatic outgrowth

Authors: Arnaldo J. Franco Torres, Jeffrey Duryea, Oliver G. McDonald

Published in: Cancer and Metastasis Reviews | Issue 2/2023

Abstract

Pancreatic cancer is a paradigm for adaptation to extreme stress. That is because genetic drivers are selected during tissue injury with epigenetic imprints encoding wound healing responses. Ironically, epigenetic memories of trauma that facilitate neoplasia can also recreate past stresses to restrain malignant progression through symbiotic tumor:stroma crosstalk. This is best exemplified by positive feedback between neoplastic chromatin outputs and fibroinflammatory stromal cues that encase malignant glands within a nutrient-deprived desmoplastic stroma. Because epigenetic imprints are chemically encoded by nutrient-derived metabolites bonded to chromatin, primary tumor metabolism adapts to preserve malignant epigenetic fidelity during starvation. Despite these adaptations, stromal stresses inevitably awaken primordial drives to seek more hospitable climates. The invasive migrations that ensue facilitate entry into the metastatic cascade. Metastatic routes present nutrient-replete reservoirs that accelerate malignant progression through adaptive metaboloepigenetics. This is best exemplified by positive feedback between biosynthetic enzymes and nutrient transporters that saturate malignant chromatin with pro-metastatic metabolite byproducts. Here we present a contemporary view of pancreatic cancer epigenetics: selection of neoplastic chromatin under fibroinflammatory pressures, preservation of malignant chromatin during starvation stresses, and saturation of metastatic chromatin by nutritional excesses that fuel lethal metastasis.

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Title: Pancreatic cancer epigenetics: adaptive metabolism reprograms starving primary tumors for widespread metastatic outgrowth
Authors: Arnaldo J. Franco Torres
Jeffrey Duryea
Oliver G. McDonald
Publication date: 15-06-2023
Publisher: Springer US
Keywords: Metastasis
Pancreatitis
Epigenetics
Pancreatic Cancer
Pancreatic Cancer
Published in: Cancer and Metastasis Reviews / Issue 2/2023
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-023-10116-z

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