The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells
Open accessAbstract
Tumor-initiating stem-like cells (TICs) are resistant to chemotherapy and associated with hepatocellular carcinoma (HCC) caused by HCV and/or alcohol-related chronic liver injury. Using HCV Tg mouse models and patients with HCC, we isolated CD133(+) TICs and identified the pluripotency marker NANOG as a direct target of TLR4, which drives the tumor-initiating activity of TICs. These TLR4/NANOG-dependent TICs were defective in the TGF-β tumor suppressor pathway. Functional oncogene screening of a TIC cDNA library identified Yap1 and Igf2bp3 as NANOG-dependent genes that inactivate TGF-β signaling. Mechanistically, we determined that YAP1 mediates cytoplasmic retention of phosphorylated SMAD3 and suppresses SMAD3 phosphorylation/activation by the IGF2BP3/AKT/mTOR pathway. Silencing of both YAP1 and IGF2BP3 restored TGF-β signaling, inhibited pluripotency genes and tumorigenesis, and abrogated chemoresistance of TICs. Mice with defective TGF-β signaling (Spnb2(+/-) mice) exhibited enhanced liver TLR4 expression and developed HCC in a TLR4-dependent manner. Taken together, these results suggest that the activated TLR4/NANOG oncogenic pathway is linked to suppression of cytostatic TGF-β signaling and could potentially serve as a therapeutic target for HCV-related HCC.
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A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF β-TRCP
Zhao, B., Li, L., Tumaneng, K., Wang, C.-Y., & Guan, K.-L. (2010) · Genes & Development · doi:10.1101/gad.1843810 · Cited by 1,418
YAP1 increases organ size and expands undifferentiated progenitor cells
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Self-citationWide spectrum of tumors in knock‐in mice carrying a Cdk4 protein insensitive to INK4 inhibitors
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Cited by
Seitz, H. K., Bataller, R., Cortez-Pinto, H., Gao, B., Gual, A., Lackner, C., Mathurin, P., Mueller, S., Szabo, G., & Tsukamoto, H. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0014-7 · Cited by 1,271
Self-citationCancer stem cells: advances in knowledge and implications for cancer therapy
Chu, X., Tian, W., Ning, J., Xiao, G., Zhou, Y., Wang, Z., Zhai, Z., Tanzhu, G., Yang, J., & Zhou, R. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01851-y · Cited by 553
Degrauwe, N., Suvà, M.-L., Janiszewska, M., Riggi, N., & Stamenkovic, I. (2016) · Genes & Development · doi:10.1101/gad.287540.116 · Cited by 324
The role of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in cancer
Lederer, M., Bley, N., Schleifer, C., & Hüttelmaier, S. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.07.006 · Cited by 287
Lai, K. K. Y., Kweon, S.-M., Chi, F., Hwang, E., Kabe, Y., Higashiyama, R., Qin, L., Yan, R., Wu, R. P., Lai, K., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.021 · Cited by 165
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Metadata
- Authors
- Chen, C.-L., Tsukamoto, H., Liu, J.-C., Kashiwabara, C., Feldman, D., Sher, L., Dooley, S., French, S. W., Mishra, L., Petrovic, L., Jeong, J. H., & Machida, K.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-06-10
- Volume
- 123
- Issue
- 7
- Pages
- 2832-2849
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2164938105
- Cited by
- 162
- References
- 6
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- bronze
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- Chen, C.-L., Tsukamoto, H., Liu, J.-C., Kashiwabara, C., Feldman, D., Sher, L., Dooley, S., French, S. W., Mishra, L., Petrovic, L., Jeong, J. H., & Machida, K. (2013). Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci65859
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