The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal Cathepsin B to promote cancer metastasis and chemoresistance
Open accessAbstract
How glucose metabolism remodels pro-tumor functions of tumor-associated macrophages (TAMs) needs further investigation. Here we show that M2-like TAMs bear the highest individual capacity to take up intratumoral glucose. Their increased glucose uptake fuels hexosamine biosynthetic pathway-dependent O-GlcNAcylation to promote cancer metastasis and chemoresistance. Glucose metabolism promotes O-GlcNAcylation of the lysosome-encapsulated protease Cathepsin B at serine 210, mediated by lysosome-localized O-GlcNAc transferase (OGT), elevating mature Cathepsin B in macrophages and its secretion in the tumor microenvironment (TME). Loss of OGT in macrophages reduces O-GlcNAcylation and mature Cathepsin B in the TME and disrupts cancer metastasis and chemoresistance. Human TAMs with high OGT are positively correlated with Cathepsin B expression, and both levels predict chemotherapy response and prognosis of individuals with cancer. Our study reports the biological and potential clinical significance of glucose metabolism in tumor-promoting TAMs and reveals insights into the underlying mechanisms.
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Cited by
De Leo, A., Ugolini, A., Yu, X., Scirocchi, F., Scocozza, D., Peixoto, B., Pace, A., D’Angelo, L., Liu, J. K. C., Etame, A. B., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.04.006 · Cited by 319
Shi, X., Wang, X., Yao, W., Shi, D., Shao, X., Lu, Z., Chai, Y., Song, J., Tang, W., & Wang, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01885-2 · Cited by 258
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Metadata
- Authors
- Shi, Q., Shen, Q., Liu, Y., Shi, Y., Huang, W., Wang, X., Li, Z., Chai, Y., Wang, H., Hu, X., Li, N., Zhang, Q., & Cao, X.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 40
- Issue
- 10
- Pages
- 1207-1222.e10
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W4297244184
- Cited by
- 334
- References
- 70
- FWCI
- 20.72
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shi, Q., Shen, Q., Liu, Y., Shi, Y., Huang, W., Wang, X., Li, Z., Chai, Y., Wang, H., Hu, X., Li, N., Zhang, Q., & Cao, X. (2022). Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal Cathepsin B to promote cancer metastasis and chemoresistance. Cancer Cell. https://doi.org/10.1016/j.ccell.2022.08.012
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