ArticleAutophagy2014
ERBB2 overexpression suppresses stress-induced autophagy and renders ERBB2-induced mammary tumorigenesis independent of monoallelic Becn1 loss.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Article
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- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Five crucial prognostic-related autophagy genes stratified female breast cancer patients aged 40-60 years.BMC bioinformatics · 2021Article
- Development and validation of a survival model for esophageal adenocarcinoma based on autophagy-associated genes.Bioengineered · 2021Article
- Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.Biomedicines · 2021Article
- Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells.Cell death & disease · 2021Article
- Regulation of Beclin 1-Mediated Autophagy by Oncogenic Tyrosine Kinases.International journal of molecular sciences · 2020Review
- Targeting Autophagy in Breast Cancer.International journal of molecular sciences · 2020Review
- RSK2 protects human breast cancer cells under endoplasmic reticulum stress through activating AMPKα2-mediated autophagy.Oncogene · 2020Article
- Article
- Beclin 1 Promotes Endosome Recruitment of Hepatocyte Growth Factor Tyrosine Kinase Substrate to Suppress Tumor Proliferation.Cancer research · 2020Article
- Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer.Frontiers in cell and developmental biology · 2020Review
- The Role of Beclin 1-Dependent Autophagy in Cancer.Biology · 2019Review
- ERBB2-modulated ATG4B and autophagic cell death in human ARPE19 during oxidative stress.PloS one · 2019Article
- The autophagic network and cancer.Nature cell biology · 2018Review
- Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy.Oxidative medicine and cellular longevity · 2018Review
- d-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer.OncoTargets and therapy · 2018Article
- Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer.Autophagy · 2018Article
- Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Defective autophagy has been implicated in mammary tumorigenesis, as the gene encoding the essential autophagy regulator BECN1 is deleted in human breast cancers and Becn1(+/-) mice develop mammary hyperplasias. In agreement with a recent study, which reports concurrent allelic BECN1 loss and ERBB2 amplification in a small number of human breast tumors, we found that low BECN1 mRNA correlates with ERBB2-overexpression in breast cancers, suggesting that BECN1 loss and ERBB2 overexpression may functionally interact in mammary tumorigenesis. We now report that ERBB2 overexpression suppressed autophagic response to stress in mouse mammary and human breast cancer cells. ERBB2-overexpressing Becn1(+/+) and Becn1(+/-) immortalized mouse mammary epithelial cells (iMMECs) formed mammary tumors in nude mice with similar kinetics, and monoallelic Becn1 loss did not alter ERBB2- and PyMT-driven mammary tumorigenesis. In human breast cancer databases, ERBB2-expressing tumors exhibit a low autophagy gene signature, independent of BECN1 mRNA expression, and have similar gene expression profiles with non-ERBB2-expressing breast tumors with low BECN1 levels. We also found that ERBB2-expressing BT474 breast cancer cells, despite being partially autophagy-deficient under stress, can be sensitized to the anti-ERBB2 antibody trastuzumab (tzb) by further pharmacological or genetic autophagy inhibition. Our results indicate that ERBB2-driven mammary tumorigenesis is associated with functional autophagy suppression and ERBB2-positive breast cancers are partially autophagy-deficient even in a wild-type BECN1 background. Furthermore and extending earlier findings using tzb-resistant cells, exogenously imposed autophagy inhibition increases the anticancer effect of trastuzumab on tzb-sensitive ERBB2-expressing breast tumor cells, indicating that pharmacological autophagy suppression has a wider role in the treatment of ERBB2-positive breast cancer.
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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.