Nanog signaling in cancer promotes stem-like phenotype and immune evasion
- Authors
- Noh, Kyung Hee; Kim, Bo Wook; Song, Kwon-Ho; Cho, Hanbyoul; Lee, Young-Ho; Kim, Jin Hee; Chung, Joon-Yong; Kim, Jae-Hoon; Hewitt, Stephen M.; Seong, Seung-Yong; Mao, Chih-Ping; Wu, T. -C.; Kim, Tae Woo
- Issue Date
- 11월-2012
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Keywords
- TUMOR-INFILTRATING LYMPHOCYTES; CELL-LIKE PROPERTIES; CERVICAL-CANCER; ANTITUMOR IMMUNITY; VACCINE POTENCY; SELF-RENEWAL; HIGH NUMBER; RESISTANCE; PATHWAY; AKT
- Citation
- JOURNAL OF CLINICAL INVESTIGATION, v.122, no.11, pp.4077 - 4093
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CLINICAL INVESTIGATION
- Volume
- 122
- Number
- 11
- Start Page
- 4077
- End Page
- 4093
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/107078
- DOI
- 10.1172/JCI64057
- ISSN
- 0021-9738
- Abstract
- Adaptation of tumor cells to the host is a major cause of cancer progression, failure of therapy, and ultimately death. Immune selection drives this adaptation in human cancer by enriching tumor cells with a cancer stem cell-like (CSC-like) phenotype that makes them resistant to CTL-mediated apoptosis; however, the mechanisms that mediate CSC maintenance and proliferation are largely unknown. Here, we report that CTL-mediated immune selection drives the evolution of tumor cells toward a CSC-like phenotype and that the CSC-like phenotype arises through the Akt signaling pathway via transcriptional induction of Tcl1a by Nanog. Furthermore, we found that hyperactivation of the Nanog/Tcl1a/Akt signaling axis was conserved across multiple types of human cancer. Inhibition of Nanog in a murine model of colon cancer rendered tumor cells susceptible to immune-mediated clearance and led to successful, long-term control of the disease. Our fmdings establish a firm link among immune selection, disease progression, and the development of a stem-like tumor phenotype in human cancer and implicate the Nanog/Tcl1a/Akt pathway as a central molecular target in this process.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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