The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism
Open accessAbstract
SUMMARY Stem cell markers such as NANOG have been implicated in various cancers; however, the functional contribution of NANOG to cancer pathogenesis has remained unclear. Here, we show that Toll-like receptor 4 (TLR4) signaling phosphorylates E2F1 to transactivate NANOG. Down-regulation of Nanog reduces tumor progression. NANOG ChIP-seq identified genes associated with NANOG-dependent mitochondrial metabolic pathways to maintain tumor-initiating stem-like cells (TICs). The causal roles of NANOG in mitochondrial metabolic reprogramming occurred through the inhibition of oxidative phosphorylation (OXPHOS) with decreased production of mitochondrial ROS and activation of fatty acid oxidation (FAO), which was required for self-renewal and drug resistance. Restoration of OXPHOS activity and inhibition of FAO rendered TICs susceptible to a standard care chemotherapy drug, sorafenib. This study provides insights into the mechanisms of NANOG-mediated generation of TICs, tumorigenesis and chemo-resistance due to metabolic reprograming of mitochondrial functions.
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Cites
Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4
Dapito, D. H., Mencin, A., Gwak, G.-Y., Pradere, J.-P., Jang, M.-K., Mederacke, I., Caviglia, J. M., Khiabanian, H., Adeyemi, A., Bataller, R., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.007 · Cited by 1,346
Machida, K., Tsukamoto, H., Mkrtchyan, H., Duan, L., Dynnyk, A., Liu, H. M., Asahina, K., Govindarajan, S., Ray, R., Ou, J.-H. J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807390106 · Cited by 223
Self-citation
Cited by
Stem cell programs in cancer initiation, progression, and therapy resistance
Huang, T., Song, X., Xu, D., Tiek, D., Goenka, A., Wu, B., Sastry, N., Hu, B., & Cheng, S.-Y. (2020) · Theranostics · doi:10.7150/thno.41648 · Cited by 524
Mechanisms of drug resistance in HCC
Ladd, A. D., Duarte, S., Sahin, I., & Zarrinpar, A. (2024) · Hepatology · doi:10.1097/hep.0000000000000237 · Cited by 363
Metabolic signatures of cancer cells and stem cells
Intlekofer, A. M., & Finley, L. W. S. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0032-0 · Cited by 322
The role of mitochondria in stem cell fate and aging
Zhang, H., Menzies, K. J., & Auwerx, J. (2018) · Development · doi:10.1242/dev.143420 · Cited by 284
STAT proteins in cancer: orchestration of metabolism
Li, Y.-J., Zhang, C., Martincuks, A., Herrmann, A., & Yu, H. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00537-3 · Cited by 282
Metadata
- Authors
- Chen, C.-L., Uthaya Kumar, D. B., Punj, V., Xu, J., Sher, L., Tahara, S. M., Hess, S., & Machida, K.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 23
- Issue
- 1
- Pages
- 206-219
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2198606871
- Cited by
- 388
- References
- 2
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- bronze
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- The paper
- Chen, C.-L., Uthaya Kumar, D. B., Punj, V., Xu, J., Sher, L., Tahara, S. M., Hess, S., & Machida, K. (2016). NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism. Cell Metabolism. https://doi.org/10.1016/j.cmet.2015.12.004
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