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Published October 6, 2020 | v3
Journal Article Open

Visualizing Subcellular Enrichment of Glycogen in Live Cancer Cells by Stimulated Raman Scattering


Glycogen, a branched glucose polymer, helps regulate glucose homeostasis through immediate storage and release of glucose. Reprogramming of glycogen metabolism has recently been suggested to play an emerging role in cancer progression and tumorigenesis. However, regulation of metabolic rewiring for glycogen synthesis and breakdown in cancer cells remains less understood. Despite the availability of various glycogen detection methods, selective visualization of glycogen in living cells with high spatial resolution has proven to be highly challenging. Here, we present an optical imaging strategy to visualize glycogen in live cancer cells with minimal perturbation by combining stimulated Raman scattering microscopy with metabolic incorporation of deuterium-labeled glucose. We revealed the subcellular enrichment of glycogen in live cancer cells and achieved specific glycogen mapping through distinct spectral identification. Using this method, different glycogen metabolic phenotypes were characterized in a series of patient-derived BRAF mutant melanoma cell lines. Our results indicate that cell lines manifesting high glycogen storage level showed increased tolerance to glucose deficiency among the studied melanoma phenotypes. This method opens up the possibility for noninvasive study of complex glycogen metabolism at subcellular resolution and may help reveal new features of glycogen regulation in cancer systems.

Additional Information

© 2020 American Chemical Society. Received: June 1, 2020; Accepted: September 9, 2020; Published: September 9, 2020. We thank Dr. Antoni Ribas for sharing the melanoma cell lines. We also thank Dr. Otto Baba and Dr. Morita for sharing the antiglycogen antibodies. We thank Dr. C. Qian, K. Miao, X. Bi, L. Lin, and Dr. L. Voong for helpful discussions. We acknowledge the following agencies and foundations for support: NIH Grant U01 CA217655 (to J.R.H.), the WA State Andy Hill CARE Foundation (to J.R.H.), and an ISB Innovator Award (Y.S.). L.W. acknowledges the support for start-up funds from California Institute of Technology. The authors declare no competing financial interest.

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Supplemental Material - ac0c02348_si_001.pdf


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November 30, 2023
November 30, 2023