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Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis
Flap endonuclease-1 (FEN1), a structure-specific nuclease participating in DNA replication and repair processes, has been confirmed to promote the proliferation and drug resistance of tumor cells. However, the biological functions of FEN1 in cancer cell migration and invasion have not been defined....
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610327/ https://www.ncbi.nlm.nih.gov/pubmed/33125141 http://dx.doi.org/10.3892/or.2020.7812 |
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author | Xu, Lu Qu, Jing-Lei Song, Na Zhang, Ling-Yun Zeng, Xue Che, Xiao-Fang Hou, Ke-Zuo Shi, Sha Feng, Zu-Ying Qu, Xiu-Juan Liu, Yun-Peng Teng, Yue-E |
author_facet | Xu, Lu Qu, Jing-Lei Song, Na Zhang, Ling-Yun Zeng, Xue Che, Xiao-Fang Hou, Ke-Zuo Shi, Sha Feng, Zu-Ying Qu, Xiu-Juan Liu, Yun-Peng Teng, Yue-E |
author_sort | Xu, Lu |
collection | PubMed |
description | Flap endonuclease-1 (FEN1), a structure-specific nuclease participating in DNA replication and repair processes, has been confirmed to promote the proliferation and drug resistance of tumor cells. However, the biological functions of FEN1 in cancer cell migration and invasion have not been defined. In the present study, using online database analysis and immunohistochemistry of the specimens, it was found that FEN1 expression was associated with a highly invasive triple-negative breast cancer (TNBC) subtype in both breast cancer samples from the Oncomine database and from patients recruited into the study. Furthermore, FEN1 was an important biomarker of lymph node metastasis and poor prognosis in patients with TNBC. FEN1 promoted migration of TNBC cell lines and FEN1 knockdown reduced the number of spontaneous lung metastasis in vivo. Ingenuity Pathway Analysis of FEN1-related transcripts in 198 patients with TNBC demonstrated that the polo-like kinase family may be the downstream target of FEN1. PLK4 was further identified as a critical target of FEN1 mediating TNBC cell migration, by regulating actin cytoskeleton rearrangement. The results of the present study validate FEN1 as a therapeutic target in patients with TNBC and revealed a new role for FEN1 in regulating TNBC invasion and metastasis. |
format | Online Article Text |
id | pubmed-7610327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-76103272020-11-04 Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis Xu, Lu Qu, Jing-Lei Song, Na Zhang, Ling-Yun Zeng, Xue Che, Xiao-Fang Hou, Ke-Zuo Shi, Sha Feng, Zu-Ying Qu, Xiu-Juan Liu, Yun-Peng Teng, Yue-E Oncol Rep Articles Flap endonuclease-1 (FEN1), a structure-specific nuclease participating in DNA replication and repair processes, has been confirmed to promote the proliferation and drug resistance of tumor cells. However, the biological functions of FEN1 in cancer cell migration and invasion have not been defined. In the present study, using online database analysis and immunohistochemistry of the specimens, it was found that FEN1 expression was associated with a highly invasive triple-negative breast cancer (TNBC) subtype in both breast cancer samples from the Oncomine database and from patients recruited into the study. Furthermore, FEN1 was an important biomarker of lymph node metastasis and poor prognosis in patients with TNBC. FEN1 promoted migration of TNBC cell lines and FEN1 knockdown reduced the number of spontaneous lung metastasis in vivo. Ingenuity Pathway Analysis of FEN1-related transcripts in 198 patients with TNBC demonstrated that the polo-like kinase family may be the downstream target of FEN1. PLK4 was further identified as a critical target of FEN1 mediating TNBC cell migration, by regulating actin cytoskeleton rearrangement. The results of the present study validate FEN1 as a therapeutic target in patients with TNBC and revealed a new role for FEN1 in regulating TNBC invasion and metastasis. D.A. Spandidos 2020-12 2020-10-16 /pmc/articles/PMC7610327/ /pubmed/33125141 http://dx.doi.org/10.3892/or.2020.7812 Text en Copyright: © Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Xu, Lu Qu, Jing-Lei Song, Na Zhang, Ling-Yun Zeng, Xue Che, Xiao-Fang Hou, Ke-Zuo Shi, Sha Feng, Zu-Ying Qu, Xiu-Juan Liu, Yun-Peng Teng, Yue-E Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis |
title | Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis |
title_full | Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis |
title_fullStr | Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis |
title_full_unstemmed | Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis |
title_short | Biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: Support of metastasis and a poor prognosis |
title_sort | biological and clinical significance of flap endonuclease-1 in triple-negative breast cancer: support of metastasis and a poor prognosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610327/ https://www.ncbi.nlm.nih.gov/pubmed/33125141 http://dx.doi.org/10.3892/or.2020.7812 |
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