한빛사 논문
Kyung Hee Noh1, Bo Wook Kim2, Kwon-Ho Song1, Hanbyoul Cho3, Young-Ho Lee1, Jin Hee Kim1, Joon-Yong Chung2, Jae-Hoon Kim3, Stephen M. Hewitt2, Seung-Yong Seong4, Chih-Ping Mao5, T-C Wu5,6,7,8,* and Tae Woo Kim1,*
1Division of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.
2Tissue Array Research Program and Applied Molecular Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
3Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
4Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
5Department of Pathology,
6Department of Obstetrics and Gynecology,
7Department of Oncology, and
8Department of Molecular Microbiology and Immunology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
*Address correspondence to: T-C Wu, Department of Pathology, Johns Hopkins School of Medicine, CRB II Room 309, 1550 Orleans Street, Baltimore, Maryland 21231, USA. Or to: Tae Woo Kim, Division of Infection and Immunology, Graduate School of Medicine, Korea University, 516 Gojan-1 Dong, Ansan-Si, Gyeonggi-Do 425-707, Seoul, Republic of Korea.
Authorship note: Kyung Hee Noh, Bo Wook Kim, Kwon-Ho Song, and Hanbyoul Cho contributed equally to this work.
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.
논문정보
관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기