Abstract

Once thought to be exclusively a storage hub for glucose, glycogen is now known to be essential in a range of physiological processes and pathological conditions. Glycogen lies at the nexus of diverse processes that promote malignancy, including proliferation, migration, invasion, and chemoresistance of cancer cells. It is also implicated in processes associated with the tumor microenvironment such as immune cell effector function and crosstalk with cancer-associated fibroblasts to promote metastasis. The enzymes of glycogen metabolism are dysregulated in a wide variety of malignancies, including cancers of the kidney, ovary, lung, bladder, liver, blood, and breast. Understanding and targeting glycogen metabolism in cancer presents a promising but under-explored therapeutic avenue. In this review, we summarize the current literature on the role of glycogen in cancer progression and discuss its potential as a therapeutic target for cancer treatment.

Highlights

  • Frontiers in OncologyGlycogen lies at the nexus of diverse processes that promote malignancy, including proliferation, migration, invasion, and chemoresistance of cancer cells

  • Glycogen is a highly branched polymer of glucose that is used for the efficient storage and release of energy [1]

  • The enzymes that mediate the rate-limiting steps of glycogen metabolism are glycogen synthase (GS), for synthesis, and PYG, for degradation [9, 10]

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Summary

Frontiers in Oncology

Glycogen lies at the nexus of diverse processes that promote malignancy, including proliferation, migration, invasion, and chemoresistance of cancer cells. It is implicated in processes associated with the tumor microenvironment such as immune cell effector function and crosstalk with cancer-associated fibroblasts to promote metastasis. The enzymes of glycogen metabolism are dysregulated in a wide variety of malignancies, including cancers of the kidney, ovary, lung, bladder, liver, blood, and breast. Understanding and targeting glycogen metabolism in cancer presents a promising but under-explored therapeutic avenue. We summarize the current literature on the role of glycogen in cancer progression and discuss its potential as a therapeutic target for cancer treatment

INTRODUCTION
Revisiting Glycogen in Cancer
REPROGRAMMED GLYCOGEN METABOLISM IN CANCER
Common Mediators of Tumor Glycogenesis
Glycogen Driving Carcinogenesis
Glycogen as a Metastatic Fuel
Glycogen and Chemoresistance
VISUALIZING AND QUANTIFYING TUMOR GLYCOGEN
PHARMACOLOGICAL DISRUPTION OF GLYCOGEN METABOLISM IN CANCER
CONCLUSION
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