API5 confers cancer stem cell-like properties through the FGF2-NANOG axis

K. H. Song, H. Cho, S. Kim, H. J. Lee, S. J. Oh, S. R. Woo, S. O. Hong, H. S. Jang, K. H. Noh, C. H. Choi, J. Y. Chung, S. M. Hewitt, J. H. Kim, M. Son, S. H. Kim, B. I. Lee, H. C. Park, Y. K. Bae, Tae Woo Kim

Research output: Contribution to journalArticle

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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 API5high human 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.

Original languageEnglish
Article numbere285
JournalOncogenesis
Volume6
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

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Neoplastic Stem Cells
Fibroblast Growth Factor 2
Apoptosis
Neoplasms
Immunologic Factors
Uterine Cervical Neoplasms
T-Lymphocytes
Phenotype
Antigens
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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API5 confers cancer stem cell-like properties through the FGF2-NANOG axis. / Song, K. H.; Cho, H.; Kim, S.; Lee, H. J.; Oh, S. J.; Woo, S. R.; Hong, S. O.; Jang, H. S.; Noh, K. H.; Choi, C. H.; Chung, J. Y.; Hewitt, S. M.; Kim, J. H.; Son, M.; Kim, S. H.; Lee, B. I.; Park, H. C.; Bae, Y. K.; Kim, Tae Woo.

In: Oncogenesis, Vol. 6, No. 1, e285, 01.01.2017.

Research output: Contribution to journalArticle

Song, KH, Cho, H, Kim, S, Lee, HJ, Oh, SJ, Woo, SR, Hong, SO, Jang, HS, Noh, KH, Choi, CH, Chung, JY, Hewitt, SM, Kim, JH, Son, M, Kim, SH, Lee, BI, Park, HC, Bae, YK & Kim, TW 2017, 'API5 confers cancer stem cell-like properties through the FGF2-NANOG axis', Oncogenesis, vol. 6, no. 1, e285. https://doi.org/10.1038/oncsis.2016.87
Song, K. H. ; Cho, H. ; Kim, S. ; Lee, H. J. ; Oh, S. J. ; Woo, S. R. ; Hong, S. O. ; Jang, H. S. ; Noh, K. H. ; Choi, C. H. ; Chung, J. Y. ; Hewitt, S. M. ; Kim, J. H. ; Son, M. ; Kim, S. H. ; Lee, B. I. ; Park, H. C. ; Bae, Y. K. ; Kim, Tae Woo. / API5 confers cancer stem cell-like properties through the FGF2-NANOG axis. In: Oncogenesis. 2017 ; Vol. 6, No. 1.
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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 API5high human 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.",
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AU - Cho, H.

AU - Kim, S.

AU - Lee, H. J.

AU - Oh, S. J.

AU - Woo, S. R.

AU - Hong, S. O.

AU - Jang, H. S.

AU - Noh, K. H.

AU - Choi, C. H.

AU - Chung, J. Y.

AU - Hewitt, S. M.

AU - Kim, J. H.

AU - Son, M.

AU - Kim, S. H.

AU - Lee, B. I.

AU - Park, H. C.

AU - Bae, Y. K.

AU - Kim, Tae Woo

PY - 2017/1/1

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