ArticleAutophagy2018
Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- ADT-OH exhibits anti-metastatic activity on triple-negative breast cancer by combinatorial targeting of autophagy and mitochondrial fission.Cell death & disease · 2024Article
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- Autophagy induced by Helicobacter Pylori infection can lead to gastric cancer dormancy, metastasis, and recurrence: new insights.Human cell · 2024Review
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- Spautin-1 Protects Against Mild TBI-Induced Anxiety-Like Behavior in Mice via Immunologically Silent Apoptosis.Neuromolecular medicine · 2023Article
- Autophagy inhibition prevents lymphatic malformation progression to lymphangiosarcoma by decreasing osteopontin and Stat3 signaling.Nature communications · 2023Article
- A review of deubiquitinases and thier roles in tumorigenesis and development.Frontiers in bioengineering and biotechnology · 2023Review
- Biglycan Promotes Cancer Stem Cell Properties, NFκB Signaling and Metastatic Potential in Breast Cancer Cells.Cancers · 2022Article
- Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma.Frontiers in oncology · 2022Article
- Enhanced ZNF521 expression induces an aggressive phenotype in human ovarian carcinoma cell lines.PloS one · 2022Article
- Five crucial prognostic-related autophagy genes stratified female breast cancer patients aged 40-60 years.BMC bioinformatics · 2021Article
- The Implication of Autophagy in Gastric Cancer Progression.Life (Basel, Switzerland) · 2021Review
- Role of autophagy in cholangiocarcinoma: An autophagy-based treatment strategy.World journal of gastrointestinal oncology · 2021Review
- A Signature of Autophagy-Related Long Non-coding RNA to Predict the Prognosis of Breast Cancer.Frontiers in genetics · 2021Article
- FIP200 Suppresses Immune Checkpoint Therapy Responses in Breast Cancers by Limiting AZI2/TBK1/IRF Signaling Independent of Its Canonical Autophagy Function.Cancer research · 2020Article
- Profound Reprogramming towards Stemness in Pancreatic Cancer Cells as Adaptation to AKT Inhibition.Cancers · 2020Article
- FAK activates AKT-mTOR signaling to promote the growth and progression of MMTV-Wnt1-driven basal-like mammary tumors.Breast cancer research : BCR · 2020Article
- Mitophagy and DNA damage signaling in human aging.Mechanisms of ageing and development · 2020Review
- Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer.Biomolecules · 2019Review
- Involvement of Actin in Autophagy and Autophagy-Dependent Multidrug Resistance in Cancer.Cancers · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Breast cancer is a heterogeneous disease, and stratification of patients is fundamental to the success of treatment modalities. Breast tumors deficient in BRCA1 are mostly associated with basal-like breast cancers and targeted therapeutics for this disease subtype are still lacking. In order to address whether macroautophagy/autophagy inhibition will be effective in BRCA1-deficient mammary tumors, we generated mice with conditional deletion of an essential autophagy gene, Rb1cc1, along with Brca1 and Trp53, through utilization of the K14-Cre transgene. We found that Rb1cc1 deletion suppressed tumorigenesis in the BRCA1-deficient model when compared to wild type and heterozygous Rb1cc1 controls. However, in contrast to previous studies in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) model, tumor growth and the distribution of histological subtypes were not affected by loss of RB1CC1. Interestingly, loss of RB1CC1 decreased mitochondrial mass and oxidative respiratory capacity of these tumor cells, along with a decrease in the phosphorylation of MTOR substrates and transcript levels of genes involved in mitochondrial biogenesis. Importantly, we observed an increased sensitivity to mitochondrial disrupting agents upon loss of RB1CC1. Consequently, our data showed that combination of an autophagy inhibitor, spautin-1, along with a mitochondrial complex I inhibitor, metformin, was more effective in limiting oxidative respiratory capacity, colony-forming ability and tumor growth. Altogether, our results indicate that inhibition of autophagy can increase the benefits of metformin treatment in BRCA1-deficient breast cancers.
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Registered trials
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.