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Non-circadian aspects of BHLHE40 cellular function in cancer
While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, brea...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289903/ https://www.ncbi.nlm.nih.gov/pubmed/32577154 http://dx.doi.org/10.18632/genesandcancer.201 |
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author | Kiss, Zsofia Mudryj, Maria Ghosh, Paramita M. |
author_facet | Kiss, Zsofia Mudryj, Maria Ghosh, Paramita M. |
author_sort | Kiss, Zsofia |
collection | PubMed |
description | While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, breast, and brain tumors; and downregulated in colorectal, esophageal, pancreatic and lung cancer. As a transcription factor, BHLHE40 is expressed in the nucleus, where it binds to target gene promoters containing the E-box hexanucleotide sequence, but can also be expressed in the cytoplasm, where it stabilizes cyclin E, preventing cyclin E-mediated DNA replication and cell cycle progression. In different organs BHLHE40 regulates different targets; hence may have different impacts on tumorigenesis. BHLHE40 promotes PI3K/Akt/mTOR activation in breast cancer, activating tumor progression, but suppresses STAT1 expression in clear cell carcinoma, triggering tumor suppression. Target specificity likely depends on cooperation with other transcription factors. BHLHE40 is activated in lung and esophageal carcinoma by the tumor suppressor p53 inducing senescence and suppressing tumor growth, but is also activated under hypoxic conditions by HIF-1α in gastric cancer and hepatocellular carcinomas, stimulating tumor progression. Thus, BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner. |
format | Online Article Text |
id | pubmed-7289903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-72899032020-06-22 Non-circadian aspects of BHLHE40 cellular function in cancer Kiss, Zsofia Mudryj, Maria Ghosh, Paramita M. Genes Cancer Review While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, breast, and brain tumors; and downregulated in colorectal, esophageal, pancreatic and lung cancer. As a transcription factor, BHLHE40 is expressed in the nucleus, where it binds to target gene promoters containing the E-box hexanucleotide sequence, but can also be expressed in the cytoplasm, where it stabilizes cyclin E, preventing cyclin E-mediated DNA replication and cell cycle progression. In different organs BHLHE40 regulates different targets; hence may have different impacts on tumorigenesis. BHLHE40 promotes PI3K/Akt/mTOR activation in breast cancer, activating tumor progression, but suppresses STAT1 expression in clear cell carcinoma, triggering tumor suppression. Target specificity likely depends on cooperation with other transcription factors. BHLHE40 is activated in lung and esophageal carcinoma by the tumor suppressor p53 inducing senescence and suppressing tumor growth, but is also activated under hypoxic conditions by HIF-1α in gastric cancer and hepatocellular carcinomas, stimulating tumor progression. Thus, BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner. Impact Journals LLC 2020 /pmc/articles/PMC7289903/ /pubmed/32577154 http://dx.doi.org/10.18632/genesandcancer.201 Text en Copyright: © 2020 Kiss et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Review Kiss, Zsofia Mudryj, Maria Ghosh, Paramita M. Non-circadian aspects of BHLHE40 cellular function in cancer |
title | Non-circadian aspects of BHLHE40 cellular function in cancer |
title_full | Non-circadian aspects of BHLHE40 cellular function in cancer |
title_fullStr | Non-circadian aspects of BHLHE40 cellular function in cancer |
title_full_unstemmed | Non-circadian aspects of BHLHE40 cellular function in cancer |
title_short | Non-circadian aspects of BHLHE40 cellular function in cancer |
title_sort | non-circadian aspects of bhlhe40 cellular function in cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289903/ https://www.ncbi.nlm.nih.gov/pubmed/32577154 http://dx.doi.org/10.18632/genesandcancer.201 |
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