Nanog signaling in cancer promotes stem-like phenotype and immune evasion

Kyung Hee Noh, Bo Wook Kim, Kwon Ho Song, Hanbyoul Cho, Young Ho Lee, Jin Hee Kim, Joon Yong Chung, Jae Hoon Kim, Stephen M. Hewitt, Seung Yong Seong, Chih Ping Mao, T. C. Wu, Tae Woo Kim

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97 Citations (Scopus)

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 findings 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.

Original languageEnglish
Pages (from-to)4077-4093
Number of pages17
JournalJournal of Clinical Investigation
Volume122
Issue number11
DOIs
Publication statusPublished - 2012 Nov 1

ASJC Scopus subject areas

  • Medicine(all)

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    Noh, K. H., Kim, B. W., Song, K. H., Cho, H., Lee, Y. H., Kim, J. H., Chung, J. Y., Kim, J. H., Hewitt, S. M., Seong, S. Y., Mao, C. P., Wu, T. C., & Kim, T. W. (2012). Nanog signaling in cancer promotes stem-like phenotype and immune evasion. Journal of Clinical Investigation, 122(11), 4077-4093. https://doi.org/10.1172/JCI64057