ArticleBreast cancer research : BCR2018
BHLHE40 confers a pro-survival and pro-metastatic phenotype to breast cancer cells by modulating HBEGF secretion.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- BHLHE40 as a transcriptional rheostat: decoding microenvironmental signals in context-dependent tumor plasticity.Science China. Life sciences · 2026Review
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Hypoxia-responsive interaction between P-TEFb, BHLHE40, and Tim8-Tim13 regulates hypoxic gene transcription.Science advances · 2026Article
- Article
- BHLHE22, targeted by deubiquitinating enzyme OTUD3, exerts an antitumor role in triple-negative breast cancer progression via transcriptionally inhibiting CDT1.Breast cancer research : BCR · 2026Article
- Digoxin targets BHLHE40 to inhibit epithelial-mesenchymal transition in cervical cancer cells via downregulation of ANGPTL3.Journal of natural medicines · 2026Article
- Multi-omics uncovers transcriptional programs of gut-resident memory CD4+ T cells in Crohn's disease.The Journal of experimental medicine · 2025Article
- Laminin-γ2-NR6A1 Fusion Protein Promotes Metastatic Potential in Non-Small-Cell Lung Carcinoma Cells without Epidermal Growth Factor Receptor Mutation.The American journal of pathology · 2025Article
- Non-cell autonomous regulation of cell-cell signaling and differentiation by mitochondrial ROS.The Journal of cell biology · 2024Article
- BHLHE40-mediated transcriptional activation of GRIN2D in gastric cancer is involved in metabolic reprogramming.Functional & integrative genomics · 2024Article
- UBTF mediates activation of L3MBTL2 to suppress NISCH expression through histone H2AK119 monoubiquitination modification in breast cancer.Clinical & experimental metastasis · 2024Article
- The Multiple Functions of HB-EGF in Female Reproduction and Related Cancer: Molecular Mechanisms and Targeting Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Long non-coding RNA NEAT1 induced by BHLHE40 activates Wnt/β-catenin signaling and potentiates colorectal cancer progression.Cell division · 2024Article
- Cancer-associated fibroblasts rewire the estrogen receptor response in luminal breast cancer, enabling estrogen independence.Oncogene · 2024Article
- Single-cell Analysis Reveals Inter- and Intratumour Heterogeneity in Metastatic Breast Cancer.Journal of mammary gland biology and neoplasia · 2023Article
- Potential Application of Self-Assembled Peptides and Proteins in Breast Cancer and Cervical Cancer.International journal of molecular sciences · 2023Review
- Cancer-Associated Fibroblast-Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- BHLHE40 Maintains the Stemness of PαS Cells In Vitro by TargetingBiomedicines · 2023Article
- The role of BHLHE40 in clinical features and prognosis value of PDAC by comprehensive analysis andFrontiers in oncology · 2023Article
- Noninvasive prediction of axillary lymph node status in breast cancer using promoter profiling of circulating cell-free DNA.Journal of translational medicine · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMetastasis is responsible for a significant number of breast cancer-related deaths. Hypoxia, a primary driving force of cancer metastasis, induces the expression of BHLHE40, a transcription regulator. This study aimed to elucidate the function of BHLHE40 in the metastatic process of breast cancer cells.
methodsTo define the role of BHLHE40 in breast cancer, BHLHE40 expression was knocked down by a lentiviral construct expressing a short hairpin RNA against BHLHE40 or knocked out by the CRISPR/Cas9 editing system. Orthotopic xenograft and experimental metastasis (tail vein injection) mouse models were used to analyze the role of BHLHE40 in lung metastasis of breast cancer. Global gene expression analysis and public database mining were performed to identify signaling pathways regulated by BHLHE40 in breast cancer. The action mechanism of BHLHE40 was examined by chromatin immunoprecipitation (ChIP), co-immunoprecipitation (CoIP), exosome analysis, and cell-based assays for metastatic potential.
resultsBHLHE40 knockdown significantly reduced primary tumor growth and lung metastasis in orthotopic xenograft and experimental metastasis models of breast cancer. Gene expression analysis implicated a role of BHLHE40 in transcriptional activation of heparin-binding epidermal growth factor (HBEGF). ChIP and CoIP assays revealed that BHLHE40 induces HBEGF transcription by blocking DNA binding of histone deacetylases (HDAC)1 and HDAC2. Cell-based assays showed that HBEGF is secreted through exosomes and acts to promote cell survival and migration. Public databases provided evidence linking high expression of BHLHE40 and HBEGF to poor prognosis of triple-negative breast cancer.
conclusionThis study reveals a novel role of BHLHE40 in promoting tumor cell survival and migration by regulating HBEGF secretion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.