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PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification
Microcalcification (MC) is a valuable diagnostic indicator of breast cancer, and it is reported to be associated with increased tumor aggressiveness and poor prognosis. Nevertheless, the exact potential molecular mechanism is not completely understood. Here, we find that the mineralized invasive bre...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643473/ https://www.ncbi.nlm.nih.gov/pubmed/37957150 http://dx.doi.org/10.1038/s41523-023-00598-z |
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author | Tian, Yao Zhao, Lu Gui, Zhengwei Liu, Shiyang Liu, Chenguang Yu, Tianyao Zhang, Lin |
author_facet | Tian, Yao Zhao, Lu Gui, Zhengwei Liu, Shiyang Liu, Chenguang Yu, Tianyao Zhang, Lin |
author_sort | Tian, Yao |
collection | PubMed |
description | Microcalcification (MC) is a valuable diagnostic indicator of breast cancer, and it is reported to be associated with increased tumor aggressiveness and poor prognosis. Nevertheless, the exact potential molecular mechanism is not completely understood. Here, we find that the mineralized invasive breast cancer (IBC) cells not only increased their proliferation and migration, but also showed the characteristic of doxorubicin resistance. The PI3K/AKT signaling pathway is associated with the generation of calcification in IBC, and it activates the transcription and translation of its downstream hypoxia-inducible factor 1α (HIF1α). Knockdown of HIF1α protein significantly downregulated cell proliferation and migration while calcification persists. Meanwhile, calcified breast cancer cells restored sensitivity to doxorubicin because of suppressed HIF1α expression. In addition, we provide initial data on the underlying value of HIF1α as a biomarker of doxorubicin resistance. These findings provide a new direction for exploring microcalcifications in IBC. |
format | Online Article Text |
id | pubmed-10643473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106434732023-11-13 PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification Tian, Yao Zhao, Lu Gui, Zhengwei Liu, Shiyang Liu, Chenguang Yu, Tianyao Zhang, Lin NPJ Breast Cancer Article Microcalcification (MC) is a valuable diagnostic indicator of breast cancer, and it is reported to be associated with increased tumor aggressiveness and poor prognosis. Nevertheless, the exact potential molecular mechanism is not completely understood. Here, we find that the mineralized invasive breast cancer (IBC) cells not only increased their proliferation and migration, but also showed the characteristic of doxorubicin resistance. The PI3K/AKT signaling pathway is associated with the generation of calcification in IBC, and it activates the transcription and translation of its downstream hypoxia-inducible factor 1α (HIF1α). Knockdown of HIF1α protein significantly downregulated cell proliferation and migration while calcification persists. Meanwhile, calcified breast cancer cells restored sensitivity to doxorubicin because of suppressed HIF1α expression. In addition, we provide initial data on the underlying value of HIF1α as a biomarker of doxorubicin resistance. These findings provide a new direction for exploring microcalcifications in IBC. Nature Publishing Group UK 2023-11-13 /pmc/articles/PMC10643473/ /pubmed/37957150 http://dx.doi.org/10.1038/s41523-023-00598-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tian, Yao Zhao, Lu Gui, Zhengwei Liu, Shiyang Liu, Chenguang Yu, Tianyao Zhang, Lin PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification |
title | PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification |
title_full | PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification |
title_fullStr | PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification |
title_full_unstemmed | PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification |
title_short | PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification |
title_sort | pi3k/akt signaling activates hif1α to modulate the biological effects of invasive breast cancer with microcalcification |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643473/ https://www.ncbi.nlm.nih.gov/pubmed/37957150 http://dx.doi.org/10.1038/s41523-023-00598-z |
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