ArticleCancer research2019
Spleen Tyrosine Kinase-Mediated Autophagy Is Required for Epithelial-Mesenchymal Plasticity and Metastasis in Breast Cancer.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2020Pooled it
- Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.Bone research · 2026Review
- Cancer-associated fibroblast-derived extracellular vesicles regulate lipophagy through PLIN2 to modulate dormancy in salivary gland adenoid cystic carcinoma cells.Experimental & molecular medicine · 2025Article
- Construction of Metastasis Prediction Models and Screening of Anti-Metastatic Drugs Based on Pan-Cancer Single-Cell EMT Features.International journal of molecular sciences · 2025Article
- Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer.Journal of translational medicine · 2025Review
- Innovative molecular targets for combatting metastasis in adrenocortical carcinoma.Frontiers in endocrinology · 2025Article
- Multi-Omics Insights into the Impact of MDH2 on Breast Cancer Progression: A Promising Druggable Target.Oncology research · 2025Article
- Protein-Sequence-Based Search of Nonreceptor ITAM-Like Regions to Identify Cytosolic Syk-Recruiting Proteins.The journal of physical chemistry. B · 2024Article
- Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic.Biomolecules · 2024Review
- Targeting autophagy: a promising approach for the treatment of breast cancer brain metastases.Clinical and translational discovery · 2024Article
- DNA-encoded probe-based assay for profiling plant kinase activities.PNAS nexus · 2024Article
- Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy.Signal transduction and targeted therapy · 2024Article
- Article
- Blockade of Syk modulates neutrophil immune-responses via the mTOR/RUBCNL-dependent autophagy pathway to alleviate intestinal inflammation in ulcerative colitis.Precision clinical medicine · 2023Article
- Syk regulates the haemocyte autophagy through inducing the mRNA expressions of autophagy-related genes and the cleavage ofFish and shellfish immunology reports · 2023Article
- Influence of CCancers · 2023Article
- Resistance to hormone therapy in breast cancer cells promotes autophagy and EGFR signaling pathway.American journal of physiology. Cell physiology · 2023Article
- Recent Advances in the Role of Autophagy in Endocrine-Dependent Tumors.Endocrine reviews · 2023Review
- ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs.Nature communications · 2023Article
- Emerging roles of endoplasmic reticulum stress in the cellular plasticity of cancer cells.Frontiers in oncology · 2023Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states contributes to their metastatic potential. Therefore, driving tumor cells into a stable mesenchymal state, as opposed to complete tumor cell eradication, presents an opportunity to pharmacologically limit disease progression by promoting an asymptomatic state of dormancy. Here, we compare a reversible model of epithelial-mesenchymal transition (EMT) induced by TGFβ to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor lapatinib. Only cells capable of returning to an epithelial phenotype resulted in skeletal metastasis. Gene expression analyses of the two mesenchymal states indicated similar transition expression profiles. A potently downregulated gene in both datasets was spleen tyrosine kinase (SYK). In contrast to this similar diminution in mRNA, kinome analyses using a peptide array and DNA-conjugated peptide substrates showed a robust increase in SYK activity upon TGFβ-induced EMT only. SYK was present in cytoplasmic RNA processing depots known as P-bodies formed during the onset of EMT, and SYK activity was required for autophagy-mediated clearance of P-bodies during mesenchymal-epithelial transition (MET). Genetic knockout of autophagy-related 7 (ATG7) or pharmacologic inhibition of SYK activity with fostamatinib, a clinically approved inhibitor of SYK, prevented P-body clearance and MET, inhibiting metastatic tumor outgrowth. Overall, this study suggests assessment of SYK activity as a biomarker for metastatic disease and the use of fostamatinib as a means to stabilize the latency of disseminated tumor cells. SIGNIFICANCE: These findings present inhibition of spleen tyrosine kinase as a therapeutic option to limit breast cancer metastasis by promoting systemic tumor dormancy.
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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.