ArticleBreast cancer research : BCR2016
MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib.
Article in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- High cyclin E1 protein, but not gene amplification, is prognostic for basal-like breast cancer.The journal of pathology. Clinical research · 2022Pooled it
- Coexisting genomic aberrations associated with lymph node metastasis in breast cancer.The Journal of clinical investigation · 2018Trial
- Endocrine therapy reprogramming of breast cancer facilitates metastatic escape via upregulation of P-Rex1/Rac1 signalling.Nature communications · 2026Article
- Whole transcriptome analysis reveals MammaPrint and BluePrint-associated gene expression patterns with early lymph node metastasis in early-stage breast cancer.Breast cancer research and treatment · 2026Observational
- Overcoming Chemotherapy Resistance in Triple-Negative Breast Cancer with Nanocarrier-Delivered siRNA Therapeutics.Journal of clinical medicine · 2026Review
- Modelling the metastatic immune microenvironment in triple-negative breast cancer.Breast cancer research : BCR · 2025Article
- Dasatinib Inhibits Basal B Breast Cancer Through ETS1-Mediated Extracellular Matrix Remodeling.Biomedicines · 2025Article
- Novel Cyanopyrimidine Derivatives as Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2025Article
- Src inhibition potentiates MCL-1 antagonist activity in acute myeloid leukemia.Signal transduction and targeted therapy · 2025Article
- Disarib, a Specific BCL2 Inhibitor, Induces Apoptosis in Triple-Negative Breast Cancer Cells and Impedes Tumour Progression in Xenografts by Altering Mitochondria-Associated Processes.International journal of molecular sciences · 2024Article
- Multi-omic profiling of simultaneous ductal carcinoma in situ and invasive breast cancer.Breast cancer research and treatment · 2024Article
- TRPA1 Contributes to FGFR2c Signaling and to Its Oncogenic Outcomes in Pancreatic Ductal Adenocarcinoma-Derived Cell Lines.Cancers · 2024Article
- Small molecule Mcl-1 inhibitor for triple negative breast cancer therapy.Frontiers in cell and developmental biology · 2024Review
- Article
- Small molecules targeting protein-protein interactions for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- A Novel Nanoemulsion Formula for an Improved Delivery of a Thalidomide Analogue to Triple-Negative Breast Cancer; Synthesis, Formulation, Characterization and Molecular Studies.International journal of nanomedicine · 2023Article
- Molecular docking analysis of MCL-1 inhibitors for breast cancer management.Bioinformation · 2023Article
- Homoharringtonine demonstrates a cytotoxic effect against triple-negative breast cancer cell lines and acts synergistically with paclitaxel.Scientific reports · 2022Article
- KRAS Mutants Upregulate Integrin β4 to Promote Invasion and Metastasis in Colorectal Cancer.Molecular cancer research : MCR · 2022Article
- The FGFR2c/PKCε Axis Controls MCL-1-Mediated Invasion in Pancreatic Ductal Adenocarcinoma Cells: Perspectives for Innovative Target Therapies.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) is an important regulator of cell survival and chemo-resistance in a wide range of malignancies, and thus its inhibition may prove to be therapeutically useful.
methodsTo examine whether targeting MCL-1 may provide an effective treatment for breast cancer, we constructed inducible models of BIMs2A expression (a specific MCL-1 inhibitor) in MDA-MB-468 (MDA-MB-468-2A) and MDA-MB-231 (MDA-MB-231-2A) cells.
resultsMCL-1 inhibition caused apoptosis of basal-like MDA-MB-468-2A cells grown as monolayers, and sensitized them to the BCL-2/BCL-XL inhibitor ABT-263, demonstrating that MCL-1 regulated cell survival. In MDA-MB-231-2A cells, grown in an organotypic model, induction of BIMs2A produced an almost complete suppression of invasion. Apoptosis was induced in such a small proportion of these cells that it could not account for the large decrease in invasion, suggesting that MCL-1 was operating via a previously undetected mechanism. MCL-1 antagonism also suppressed local invasion and distant metastasis to the lung in mouse mammary intraductal xenografts. Kinomic profiling revealed that MCL-1 antagonism modulated Src family kinases and their targets, which suggested that MCL-1 might act as an upstream modulator of invasion via this pathway. Inhibition of MCL-1 in combination with dasatinib suppressed invasion in 3D models of invasion and inhibited the establishment of tumors in vivo.
conclusionThese data provide the first evidence that MCL-1 drives breast cancer cell invasion and suggests that MCL-1 antagonists could be used alone or in combination with drugs targeting Src kinases such as dasatinib to suppress metastasis.
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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.