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; T. W. Kim

doi:10.1038/oncsis.2016.87

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, T. W. Kim

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

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 language	English
Article number	e285
Journal	Oncogenesis
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/oncsis.2016.87
Publication status	Published - 2017

Bibliographical note

Funding Information:
Tissue microarrays containing four 1.0 mm cores from 479 formalin-fixed, paraffin-embedded cervical neoplasia tissue specimens and matched nonadjacent normal cervical epithelial tissue specimens, have been previously described. Tissue specimens were prospectively collected from patients who were admitted to Gangnam Severance Hospital between 1996 and 2010. Some of the paraffin blocks were provided by the Korea Gynecologic Cancer Bank through the Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea (NRF-2012M3A9B8021800). Tissue samples were collected from patients who provided informed consent. This study was approved by the Institutional Review Board of Gangnam Severance Hospital (Seoul, South Korea) and it was additionally approved by the Office of Human Subjects Research at the National Institutes of Health.

Funding Information:
This work was funded by the National Research Foundation of Korea (NRF-2014R1A2A1A10054205 and NRF-2013M3A9D3045881).

ASJC Scopus subject areas

Molecular Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/oncsis.2016.87

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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, T. W. (2017). API5 confers cancer stem cell-like properties through the FGF2-NANOG axis. Oncogenesis, 6(1), Article e285. https://doi.org/10.1038/oncsis.2016.87

@article{49d8ca0f33964d3681be9cb443c8d371,

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 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.",

author = "Song, {K. H.} and H. Cho and S. Kim and Lee, {H. J.} and Oh, {S. J.} and Woo, {S. R.} and Hong, {S. O.} and Jang, {H. S.} and Noh, {K. H.} and Choi, {C. H.} and Chung, {J. Y.} and Hewitt, {S. M.} and Kim, {J. H.} and M. Son and Kim, {S. H.} and Lee, {B. I.} and Park, {H. C.} and Bae, {Y. K.} and Kim, {T. W.}",

note = "Funding Information: Tissue microarrays containing four 1.0 mm cores from 479 formalin-fixed, paraffin-embedded cervical neoplasia tissue specimens and matched nonadjacent normal cervical epithelial tissue specimens, have been previously described. Tissue specimens were prospectively collected from patients who were admitted to Gangnam Severance Hospital between 1996 and 2010. Some of the paraffin blocks were provided by the Korea Gynecologic Cancer Bank through the Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea (NRF-2012M3A9B8021800). Tissue samples were collected from patients who provided informed consent. This study was approved by the Institutional Review Board of Gangnam Severance Hospital (Seoul, South Korea) and it was additionally approved by the Office of Human Subjects Research at the National Institutes of Health. Funding Information: This work was funded by the National Research Foundation of Korea (NRF-2014R1A2A1A10054205 and NRF-2013M3A9D3045881).",

year = "2017",

doi = "10.1038/oncsis.2016.87",

language = "English",

volume = "6",

journal = "Oncogenesis",

issn = "2157-9024",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - API5 confers cancer stem cell-like properties through the FGF2-NANOG axis

AU - Song, K. H.

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, T. W.

N1 - Funding Information: Tissue microarrays containing four 1.0 mm cores from 479 formalin-fixed, paraffin-embedded cervical neoplasia tissue specimens and matched nonadjacent normal cervical epithelial tissue specimens, have been previously described. Tissue specimens were prospectively collected from patients who were admitted to Gangnam Severance Hospital between 1996 and 2010. Some of the paraffin blocks were provided by the Korea Gynecologic Cancer Bank through the Bio & Medical Technology Development Program of the Ministry of Education, Science and Technology, Korea (NRF-2012M3A9B8021800). Tissue samples were collected from patients who provided informed consent. This study was approved by the Institutional Review Board of Gangnam Severance Hospital (Seoul, South Korea) and it was additionally approved by the Office of Human Subjects Research at the National Institutes of Health. Funding Information: This work was funded by the National Research Foundation of Korea (NRF-2014R1A2A1A10054205 and NRF-2013M3A9D3045881).

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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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U2 - 10.1038/oncsis.2016.87

DO - 10.1038/oncsis.2016.87

M3 - Article

AN - SCOPUS:85038960854

SN - 2157-9024

VL - 6

JO - Oncogenesis

JF - Oncogenesis

IS - 1

M1 - e285

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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