ArticleScience signaling2018
Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Functionalized biomaterial platforms for interventional embolization therapy of hepatocellular carcinoma.Bioactive materials · 2027Review
- Targeting ABL kinases overcomes melanoma immune evasion following resistance to MAPK inhibition.Nature communications · 2026Article
- drGT: interpretable drug response prediction with attention-guided gene attribution on a drug-cell-gene heterogeneous graph.BMC bioinformatics · 2026Article
- Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer.Cancers · 2026Review
- Phenotype switching in highly invasive resistant to vemurafenib and cobimetinib melanoma cells.Cell communication and signaling : CCS · 2025Article
- drGT: Attention-Guided Gene Assessment of Drug Response Utilizing a Drug-Cell-Gene Heterogeneous Network.ArXiv · 2025Article
- From Molecular Therapies to Lysosomal Transplantation and Targeted Drug Strategies: Present Applications, Limitations, and Future Prospects of Lysosomal Medications.Biomolecules · 2025Review
- Association between cathepsins and skin cancers: A bidirectional two-sample Mendelian randomization study.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
- Quantitative Proteomics Reveal That CB2R Agonist JWH-133 Downregulates NF-κB Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages.International journal of molecular sciences · 2024Article
- ABL1/2 and DDR1 Drive MEKi Resistance in NRAS-Mutant Melanomas by Stabilizing RAF/MYC/ETS1 and Promoting RAF Homodimerization.Cancers · 2023Article
- Review
- Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia.Cancers · 2022Review
- Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of COVID-19.Frontiers in pharmacology · 2022Review
- Drug repurposing of ivermectin abrogates neutrophil extracellular traps and prevents melanoma metastasis.Frontiers in oncology · 2022Article
- Predicting Diagnostic Potential of Cathepsin in Epithelial Ovarian Cancer: A Design Validated by Computational, Biophysical and Electrochemical Data.Biomolecules · 2021Article
- Targeting lysosomes in human disease: from basic research to clinical applications.Signal transduction and targeted therapy · 2021Review
- Therapeutic approaches for SARS-CoV-2 infection.Methods (San Diego, Calif.) · 2021Review
- Role of the ABL tyrosine kinases in the epithelial-mesenchymal transition and the metastatic cascade.Cell communication and signaling : CCS · 2021Review
- Targeting Pan-ETS Factors Inhibits Melanoma Progression.Cancer research · 2021Article
- Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The incidence of melanoma is increasing, particularly in young women, and the disease remains incurable for many because of its aggressive, metastatic nature and its high rate of resistance to conventional, targeted, and immunological agents. Cathepsins are proteases that are critical for melanoma progression and therapeutic resistance. Intracellular cathepsins cleave or degrade proteins that restrict cancer progression, whereas extracellular cathepsins directly cleave the extracellular matrix and activate proinvasive proteases in the tumor microenvironment. Cathepsin secretion is markedly increased in cancer cells. We investigated the signaling pathways leading to increased cathepsin secretion in melanoma cells. We found that the nonreceptor tyrosine kinases Abl and Arg (Abl/Arg) promoted the secretion of cathepsin B and cathepsin L by activating transcription factors (namely, Ets1, Sp1, and NF-κB/p65) that have key roles in the epithelial-mesenchymal transition (EMT), invasion, and therapeutic resistance. In some melanoma cell lines, Abl/Arg promoted the Ets1/p65-induced secretion of cathepsin B and cathepsin L in a kinase-independent manner, whereas in other melanoma lines, Abl/Arg promoted the kinase-dependent, Sp1/Ets1/p65-mediated induction of cathepsin L secretion and the Sp1/p65-mediated induction of cathepsin B secretion. As an indication of clinical relevance, the abundance of mRNAs encoding Abl/Arg, Sp1, Ets1, and cathepsins was positively correlated in primary melanomas, and Abl/Arg-driven invasion in culture and metastasis in vivo required cathepsin secretion. These data suggest that drugs targeting Abl kinases, many of which are FDA-approved, might inhibit cathepsin secretion in some melanomas and potentially other aggressive cancers harboring activated Abl kinases.
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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 Socratic graph.