Non-circadian aspects of BHLHE40 cellular function in cancer
Autor: | Paramita M. Ghosh, Maria Mudryj, Zsofia Kiss |
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Rok vydání: | 2020 |
Předmět: |
AMPK
0301 basic medicine Cancer Research Cyclin E HIF-1α E-box Review Biology medicine.disease_cause 03 medical and health sciences Rare Diseases 0302 clinical medicine Breast Cancer Genetics medicine Lung Transcription factor PI3K/AKT/mTOR pathway Cancer Lung Cancer BHLHE40/DEC1/STRA13/SHARP2 medicine.disease DEC1 030104 developmental biology Tumor progression 030220 oncology & carcinogenesis Cancer research PI3K/Akt/mTOR Digestive Diseases Carcinogenesis |
Zdroj: | Genes & cancer, vol 11, iss 1-2 Genes & Cancer |
ISSN: | 1947-6027 |
Popis: | 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. |
Databáze: | OpenAIRE |
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