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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2024

Open Access 01-12-2024 | Review

cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment

Authors: Hongying Zhang, Yongliang Liu, Jieya Liu, Jinzhu Chen, Jiao Wang, Hui Hua, Yangfu Jiang

Published in: Journal of Hematology & Oncology | Issue 1/2024

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Abstract

Cancer is a complex disease resulting from abnormal cell growth that is induced by a number of genetic and environmental factors. The tumor microenvironment (TME), which involves extracellular matrix, cancer-associated fibroblasts (CAF), tumor-infiltrating immune cells and angiogenesis, plays a critical role in tumor progression. Cyclic adenosine monophosphate (cAMP) is a second messenger that has pleiotropic effects on the TME. The downstream effectors of cAMP include cAMP-dependent protein kinase (PKA), exchange protein activated by cAMP (EPAC) and ion channels. While cAMP can activate PKA or EPAC and promote cancer cell growth, it can also inhibit cell proliferation and survival in context- and cancer type-dependent manner. Tumor-associated stromal cells, such as CAF and immune cells, can release cytokines and growth factors that either stimulate or inhibit cAMP production within the TME. Recent studies have shown that targeting cAMP signaling in the TME has therapeutic benefits in cancer. Small-molecule agents that inhibit adenylate cyclase and PKA have been shown to inhibit tumor growth. In addition, cAMP-elevating agents, such as forskolin, can not only induce cancer cell death, but also directly inhibit cell proliferation in some cancer types. In this review, we summarize current understanding of cAMP signaling in cancer biology and immunology and discuss the basis for its context-dependent dual role in oncogenesis. Understanding the precise mechanisms by which cAMP and the TME interact in cancer will be critical for the development of effective therapies. Future studies aimed at investigating the cAMP-cancer axis and its regulation in the TME may provide new insights into the underlying mechanisms of tumorigenesis and lead to the development of novel therapeutic strategies.
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Metadata
Title
cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment
Authors
Hongying Zhang
Yongliang Liu
Jieya Liu
Jinzhu Chen
Jiao Wang
Hui Hua
Yangfu Jiang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2024
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-024-01524-x

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