ArticleOncogene2015
Loss of the E3 ubiquitin ligase HACE1 results in enhanced Rac1 signaling contributing to breast cancer progression.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Article
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- The role of RAC1 in resistance to targeted therapies in cancer.Small GTPases · 2024Review
- RABV induces biphasic actin cytoskeletal rearrangement through Rac1 activity modulation.Journal of virology · 2024Article
- Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1.Nature structural & molecular biology · 2024Article
- Article
- Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Chaperone-Dependent Degradation of Cdc42 Promotes Cell Polarity and Shields the Protein from Aggregation.Molecular and cellular biology · 2023Article
- Regulation of Cdc42 protein turnover modulates the filamentous growth MAPK pathway.The Journal of cell biology · 2022Article
- HACE1-mediated NRF2 activation causes enhanced malignant phenotypes and decreased radiosensitivity of glioma cells.Signal transduction and targeted therapy · 2021Article
- RAC1 plays an essential role in estrogen receptor alpha function in breast cancer cells.Oncogene · 2021Article
- An Update on the Role of Ubiquitination in Melanoma Development and Therapies.Journal of clinical medicine · 2021Review
- Article
- The interplay of Rac1 activity, ubiquitination and GDI binding and its consequences for endothelial cell spreading.PloS one · 2021Article
- Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses.Cells · 2020Review
- HACE1 Prevents Lung Carcinogenesis via Inhibition of RAC-Family GTPases.Cancer research · 2020Article
- Structural insights into a HECT-type E3 ligase AREL1 and its ubiquitination activitiesThe Journal of biological chemistry · 2019Article
- RHO Family GTPases in the Biology of Lymphoma.Cells · 2019Review
- Ubiquitination and Long Non-coding RNAs Regulate Actin Cytoskeleton Regulators in Cancer Progression.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transition from ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC) is a crucial step in breast cancer progression. The specific alterations that govern this transition have not been elucidated. HER2/neu is frequently overexpressed in DCIS but is less common in IBC, thereby suggesting additional requirements for transformation. To identify genes capable of cooperating with HER2/neu to fully transform mammary epithelial cells, we used an insertional mutagenesis screen on cells isolated from wild-type neu expressing mice and identified the E3 ligase HACE1 as HER2 cooperative tumor suppressor gene. Loss of HACE1 expression is commonly seen in clinical breast cancer data sets. HACE1 downregulation in normal human mammary epithelial cells (HMECs) results in the accumulation of the activated GTP-bound Rac1 partially transforming these cells. Overexpression of HER2 activates Rac1, which further accumulates upon HACE1 loss resulting in Rac1 hyperactivation. Although the knockdown of HACE1 or overexpression of HER2 alone in HMECs is not sufficient for tumorigenesis, HER2 overexpression combined with HACE1 downregulation fully transforms HMECs resulting in robust tumor formation. The pharmaceutical interference of Rac function abrogates the effects of HACE1 loss both in vitro and in vivo, resulting in marked reduction in tumor burden. Our work supports a critical role for HACE1 in breast cancer progression and identifies patients that may benefit from Rac-targeted therapies.
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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.