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Review
. 2021 Jul 22;11(8):1082.
doi: 10.3390/biom11081082.

Epigenetic Alterations in Pancreatic Cancer Metastasis

Sarah S Wang  1   2 , Jihao Xu  1   2 , Keely Y Ji  1 , Chang-Il Hwang  1   2   3
Affiliations
Review

Epigenetic Alterations in Pancreatic Cancer Metastasis

Sarah S Wang et al. Biomolecules. .

Abstract

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Pancreatic ductal adenocarcinoma (PDA) is the most common (90%) and aggressive type of pancreatic cancer. Genomic analyses of PDA specimens have identified the recurrent genetic mutations that drive PDA initiation and progression. However, the underlying mechanisms that further drive PDA metastasis remain elusive. Despite many attempts, no recurrent genetic mutation driving PDA metastasis has been found, suggesting that PDA metastasis is driven by epigenetic fluctuations rather than genetic factors. Therefore, establishing epigenetic mechanisms of PDA metastasis would facilitate the development of successful therapeutic interventions. In this review, we provide a comprehensive overview on the role of epigenetic mechanisms in PDA as a critical contributor on PDA progression and metastasis. In particular, we explore the recent advancements elucidating the role of nucleosome remodeling, histone modification, and DNA methylation in the process of cancer metastasis.

Keywords: DNA methylation; epigenetics; metastasis; pancreatic cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration showing pancreatic ductal adenocarcinoma (PDA) progression from the normal pancreas, pancreatic intraepithelial neoplasia (PanIN), and metastasis. Early pancreatic carcinogenesis is driven by genetic alterations in KRAS, CDKN2A, TP53, and SMAD4 (top). During metastasis, PDA cells penetrate the blood vessel (intravasation), circulate through the bloodstream, invade into the metastatic site (extravasation), and colonize to form a secondary malignant tumor. The process of pancreatic cancer metastasis is facilitated by epigenetic alterations (bottom).
Figure 2
Figure 2
Summary of the epigenetic mechanisms behind PDA metastasis. Metastatic PDA tumors have aberrant epigenetic profiles that are different from PDA primary tumors. Nucleosome remodeling and histone modification (e.g., acetylation of histone 3 lysine 9) increase chromatin accessibility, allowing for transcription factor binding and gene transcription. On the other hand, DNA methylation of CpG islands leads to gene repression. These processes are mediated by epigenetic regulators, some of which are noted in the figure.
See this image and copyright information in PMC

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