title: API5 confers cancer stem cell-like properties through the FGF2-NANOG axis.
abstract: Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity. Critically, these CSC-like properties mediated by API5 are dependent on FGFR1 signaling, which is triggered by E2F1-dependent FGF2 expression. Furthermore, we uncovered the FGF2-NANOG molecular axis as a downstream component of API5 signaling that is conserved in cervical cancer patients. Finally, we found that the blockade of FGFR signaling is an effective strategy to control API5highhuman cancer. Thus, our findings reveal a crucial role of API5 in linking immune resistance and CSC-like properties, and provide the rationale for its therapeutic application for the treatment of API5+refractory tumors.
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: K-H
authors.initials: KH
authors.lastname: Song
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.|Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.|Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Cho
authors.affiliation: Graduate School of Medicine, Korea University, Ansan, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: S R
authors.initials: SR
authors.lastname: Woo
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: S-O
authors.initials: SO
authors.lastname: Hong
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Jang
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Noh
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.|Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Choi
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.|Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Son
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biothechnology (KRIBB), Daejeon, Republic of Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Biomolecular Function Research Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Goyang, Republic of Korea.
authors.forename: B I
authors.initials: BI
authors.lastname: Lee
authors.affiliation: Graduate School of Medicine, Korea University, Ansan, Republic of Korea.
authors.forename: H-C
authors.initials: HC
authors.lastname: Park
authors.affiliation: Comparative Biomedical Research Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Bae
authors.affiliation: Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.|Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: T W
authors.initials: TW
authors.lastname: Kim