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Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer
Focal adhesion kinase (FAK) activation has been reported to be associated with cell progression and metastasis in a wide variety of cancer cells. Target treatment by inhibiting FAK has achieved remarkable effects in several cancers, but the effect in ovarian cancer has not been reported. In this stu...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777525/ https://www.ncbi.nlm.nih.gov/pubmed/35201437 http://dx.doi.org/10.1007/s12672-021-00425-6 |
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author | Li, Hong Gao, Yizhi Ren, Chenchen |
author_facet | Li, Hong Gao, Yizhi Ren, Chenchen |
author_sort | Li, Hong |
collection | PubMed |
description | Focal adhesion kinase (FAK) activation has been reported to be associated with cell progression and metastasis in a wide variety of cancer cells. Target treatment by inhibiting FAK has achieved remarkable effects in several cancers, but the effect in ovarian cancer has not been reported. In this study, we determined the role and the underlying molecular mechanism of BI853520, a novel small chemical FAK inhibitor against ovarian cancer. Results show that phosphorylated FAK tyrosine 397 (p-FAK Y397) is highly expressed in ovarian cancer tumor tissues and cell lines (SKOV3 and OVCAR3). BI853520 treatment greatly suppresses cell proliferation, viability, migration, invasion, decreases anchorage-independent growth and motility in vitro. Besides, treatment with BI853520 increases biologic effects following combination with chemotherapy in ovarian cancer cell lines. In addition, BI853520 suppresses EMT in ovarian cancer cell lines. Mechanically, BI853520 treatment downregulates the activation of PI3K/AKT/mTOR signal pathway. Finally, mice model experiments confirm BI853520 treatment dramatically reduces tumor growth in vivo and suppresses the activation of PI3K/AKT/mTOR signal pathway. Taken together, our findings demonstrate that focal adhesion kinase inhibitor BI853520 inhibits cell proliferation, migration, invasion and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer, and BI853520 can offer a preclinical rationale for targeting repression of FAK in ovarian cancer. |
format | Online Article Text |
id | pubmed-8777525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-87775252022-02-03 Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer Li, Hong Gao, Yizhi Ren, Chenchen Discov Oncol Research Focal adhesion kinase (FAK) activation has been reported to be associated with cell progression and metastasis in a wide variety of cancer cells. Target treatment by inhibiting FAK has achieved remarkable effects in several cancers, but the effect in ovarian cancer has not been reported. In this study, we determined the role and the underlying molecular mechanism of BI853520, a novel small chemical FAK inhibitor against ovarian cancer. Results show that phosphorylated FAK tyrosine 397 (p-FAK Y397) is highly expressed in ovarian cancer tumor tissues and cell lines (SKOV3 and OVCAR3). BI853520 treatment greatly suppresses cell proliferation, viability, migration, invasion, decreases anchorage-independent growth and motility in vitro. Besides, treatment with BI853520 increases biologic effects following combination with chemotherapy in ovarian cancer cell lines. In addition, BI853520 suppresses EMT in ovarian cancer cell lines. Mechanically, BI853520 treatment downregulates the activation of PI3K/AKT/mTOR signal pathway. Finally, mice model experiments confirm BI853520 treatment dramatically reduces tumor growth in vivo and suppresses the activation of PI3K/AKT/mTOR signal pathway. Taken together, our findings demonstrate that focal adhesion kinase inhibitor BI853520 inhibits cell proliferation, migration, invasion and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer, and BI853520 can offer a preclinical rationale for targeting repression of FAK in ovarian cancer. Springer US 2021-08-30 /pmc/articles/PMC8777525/ /pubmed/35201437 http://dx.doi.org/10.1007/s12672-021-00425-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Li, Hong Gao, Yizhi Ren, Chenchen Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer |
title | Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer |
title_full | Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer |
title_fullStr | Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer |
title_full_unstemmed | Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer |
title_short | Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer |
title_sort | focal adhesion kinase inhibitor bi 853520 inhibits cell proliferation, migration and emt process through pi3k/akt/mtor signaling pathway in ovarian cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777525/ https://www.ncbi.nlm.nih.gov/pubmed/35201437 http://dx.doi.org/10.1007/s12672-021-00425-6 |
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