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

Lee, Dongkwan and Du, Jiajun and Yu, Rona and Su, Yapeng and Heath, James R. and Wei, Lu (2020) Visualizing Subcellular Enrichment of Glycogen in Live Cancer Cells by Stimulated Raman Scattering. Analytical Chemistry, 92 (19). pp. 13182-13191. ISSN 0003-2700.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription
Su, Yapeng0000-0002-6305-8467
Heath, James R.0000-0001-5356-4385
Wei, Lu0000-0001-9170-2283
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.
Funding AgencyGrant Number
NIHU01 CA217655
Andy Hill CARE FoundationUNSPECIFIED
Institute for Systems BiologyUNSPECIFIED
Issue or Number:19
Record Number:CaltechAUTHORS:20200911-133137005
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Official Citation:Visualizing Subcellular Enrichment of Glycogen in Live Cancer Cells by Stimulated Raman Scattering. Dongkwan Lee, Jiajun Du, Rona Yu, Yapeng Su, James R. Heath, and Lu Wei. Analytical Chemistry 2020 92 (19), 13182-13191; DOI: 10.1021/acs.analchem.0c02348
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105346
Deposited By: George Porter
Deposited On:14 Sep 2020 14:16
Last Modified:07 Oct 2020 21:56

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