Metastasis is altered through multiple processes regulated by the E2F1 transcription factor

Abstract The E2F family of transcription factors is important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis and metastasis. Alteration of the Rb/E2F pathway occurs in various forms of cancer, including breast cancer. E2F1 ablation has...

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Autores principales:	Matthew R. Swiatnicki, Eran R. Andrechek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cd3d8c51cc584568b05e926126d6c529
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spelling	oai:doaj.org-article:cd3d8c51cc584568b05e926126d6c5292021-12-02T14:49:43ZMetastasis is altered through multiple processes regulated by the E2F1 transcription factor10.1038/s41598-021-88924-y2045-2322https://doaj.org/article/cd3d8c51cc584568b05e926126d6c5292021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88924-yhttps://doaj.org/toc/2045-2322Abstract The E2F family of transcription factors is important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis and metastasis. Alteration of the Rb/E2F pathway occurs in various forms of cancer, including breast cancer. E2F1 ablation has been shown to decrease metastasis in MMTV-Neu and MMTV-PyMT transgenic mouse models of breast cancer. Here we take a bioinformatic approach to determine the E2F1 regulated genomic alterations involved in the metastatic cascade, in both Neu and PyMT models. Through gene expression analysis, we reveal few transcriptome changes in non-metastatic E2F1−/− tumors relative to transgenic tumor controls. However investigation of these models through whole genome sequencing found numerous differences between the models, including differences in the proposed tumor etiology between E2F1−/− and E2F1+/+ tumors induced by Neu or PyMT. For example, loss of E2F1 within the Neu model led to an increased contribution of the inefficient double stranded break repair signature to the proposed etiology of the tumors. While the SNV mutation burden was higher in PyMT mouse tumors than Neu mouse tumors, there was no statistically significant differences between E2F WT and E2F1 KO mice. Investigating mutated genes through gene set analysis also found a significant number of genes mutated in the cell adhesion pathway in E2F1−/− tumors, indicating this may be a route for disruption of metastasis in E2F1−/− tumors. Overall, these findings illustrate the complicated nature of uncovering drivers of the metastatic process.Matthew R. SwiatnickiEran R. AndrechekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew R. Swiatnicki Eran R. Andrechek Metastasis is altered through multiple processes regulated by the E2F1 transcription factor
description	Abstract The E2F family of transcription factors is important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis and metastasis. Alteration of the Rb/E2F pathway occurs in various forms of cancer, including breast cancer. E2F1 ablation has been shown to decrease metastasis in MMTV-Neu and MMTV-PyMT transgenic mouse models of breast cancer. Here we take a bioinformatic approach to determine the E2F1 regulated genomic alterations involved in the metastatic cascade, in both Neu and PyMT models. Through gene expression analysis, we reveal few transcriptome changes in non-metastatic E2F1−/− tumors relative to transgenic tumor controls. However investigation of these models through whole genome sequencing found numerous differences between the models, including differences in the proposed tumor etiology between E2F1−/− and E2F1+/+ tumors induced by Neu or PyMT. For example, loss of E2F1 within the Neu model led to an increased contribution of the inefficient double stranded break repair signature to the proposed etiology of the tumors. While the SNV mutation burden was higher in PyMT mouse tumors than Neu mouse tumors, there was no statistically significant differences between E2F WT and E2F1 KO mice. Investigating mutated genes through gene set analysis also found a significant number of genes mutated in the cell adhesion pathway in E2F1−/− tumors, indicating this may be a route for disruption of metastasis in E2F1−/− tumors. Overall, these findings illustrate the complicated nature of uncovering drivers of the metastatic process.
format	article
author	Matthew R. Swiatnicki Eran R. Andrechek
author_facet	Matthew R. Swiatnicki Eran R. Andrechek
author_sort	Matthew R. Swiatnicki
title	Metastasis is altered through multiple processes regulated by the E2F1 transcription factor
title_short	Metastasis is altered through multiple processes regulated by the E2F1 transcription factor
title_full	Metastasis is altered through multiple processes regulated by the E2F1 transcription factor
title_fullStr	Metastasis is altered through multiple processes regulated by the E2F1 transcription factor
title_full_unstemmed	Metastasis is altered through multiple processes regulated by the E2F1 transcription factor
title_sort	metastasis is altered through multiple processes regulated by the e2f1 transcription factor
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cd3d8c51cc584568b05e926126d6c529
work_keys_str_mv	AT matthewrswiatnicki metastasisisalteredthroughmultipleprocessesregulatedbythee2f1transcriptionfactor AT eranrandrechek metastasisisalteredthroughmultipleprocessesregulatedbythee2f1transcriptionfactor
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Metastasis is altered through multiple processes regulated by the E2F1 transcription factor

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