ArticleOncogene2014
c-Abl and Arg induce cathepsin-mediated lysosomal degradation of the NM23-H1 metastasis suppressor in invasive cancer.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation.Scientific reports · 2024Article
- 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
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer.British journal of cancer · 2023Article
- ABL1/2 and DDR1 Drive MEKi Resistance in NRAS-Mutant Melanomas by Stabilizing RAF/MYC/ETS1 and Promoting RAF Homodimerization.Cancers · 2023Article
- Lysosomes, curcumin, and anti-tumor effects: how are they linked?Frontiers in pharmacology · 2023Review
- Regulation of metastasis suppressor NME1 by a key metabolic cofactor coenzyme A.Redox biology · 2021Article
- Loss of the Metastasis Suppressor NME1, But Not of Its Highly Related Isoform NME2, Induces a Hybrid Epithelial-Mesenchymal State in Cancer Cells.International journal of molecular sciences · 2021Article
- CTCF and EGR1 suppress breast cancer cell migration through transcriptional control of Nm23-H1.Scientific reports · 2021Article
- The role of lysosomes in cancer development and progression.Cell & bioscience · 2020Review
- Mutations at the dimer interface and surface residues of Nm23-H1 metastasis suppressor affect its expression and function.Molecular and cellular biochemistry · 2020Article
- Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling.Nature communications · 2020Article
- The Function of NM23-H1/NME1 and Its Homologs in Major Processes Linked to Metastasis.Pathology oncology research : POR · 2020Review
- Expression profiles of p53/p73, NME and GLI families in metastatic melanoma tissue and cell lines.Scientific reports · 2019Article
- Helicobacter pylori-controlled c-Abl localization promotes cell migration and limits apoptosis.Cell communication and signaling : CCS · 2019Article
- Inhibition effects of Yuxiao San combined with cisplatin on transplanted tumor growths via upregulation of nm-23 and downregulation of K-ras in Lewis lung cancer mice.Oncology letters · 2019Article
- Potential protein markers for breast cancer recurrence: a retrospective cohort study.Cancer causes & control : CCC · 2019Article
- The metastasis suppressor NME1 inhibits melanoma cell motility via direct transcriptional induction of the integrin beta-3 gene.Experimental cell research · 2019Article
- Metastasis Suppressor NME1 Directly Activates Transcription of theAnticancer research · 2018Article
- EnABLing Tumor Growth and Progression: Recent progress in unraveling the functions of ABL kinases in solid tumor cells.Current pharmacology reports · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Metastasis suppressors comprise a growing class of genes whose downregulation triggers metastatic progression. In contrast to tumor suppressors, metastasis suppressors are rarely mutated or deleted, and little is known regarding the mechanisms by which their expression is downregulated. Here, we demonstrate that the metastasis suppressor, NM23-H1, is degraded by lysosomal cysteine cathepsins (L,B), which directly cleave NM23-H1. In addition, activation of c-Abl and Arg oncoproteins induces NM23-H1 degradation in invasive cancer cells by increasing cysteine cathepsin transcription and activation. Moreover, c-Abl activates cathepsins by promoting endosome maturation, which facilitates trafficking of NM23-H1 to the lysosome where it is degraded. Importantly, the invasion- and metastasis-promoting activity of c-Abl/Arg is dependent on their ability to induce NM23-H1 degradation, and the pathway is clinically relevant as c-Abl/Arg activity and NM23-H1 expression are inversely correlated in primary breast cancers and melanomas. Thus, we demonstrate a novel mechanism by which cathepsin expression is upregulated in cancer cells (via Abl kinases). We also identify a novel role for intracellular cathepsins in invasion and metastasis (degradation of a metastasis suppressor). Finally, we identify novel crosstalk between oncogenic and metastasis suppressor pathways, thereby providing mechanistic insight into the process of NM23-H1 loss, which may pave the way for new strategies to restore NM23-H1 expression and block metastatic progression.
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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.