ArticleJournal of translational medicine2025
Melanophilin inhibit the growth and lymph node metastasis of triple negative breast cancer via the NONO-SPHK1-S1P axis.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Sphingosine-1-phosphate induces angiogenesis via the activating STAT3 signaling pathway to drive colorectal cancer progression.Journal of gastrointestinal oncology · 2026Article
- MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Causal relationship and pathogenic mechanism analysis of breast cancer and coronary heart disease based on mendelian randomization and transcriptome data analysis.Immunogenetics · 2026Article
- Integrative genomic profiling identifies MLPH as a candidate gene in prostate cancer.Frontiers in medicine · 2026Article
- The SP1-SuperEnhancer-SPHK1 Axis Mediates Niraparib Resistance in TNBC.Pharmaceuticals (Basel, Switzerland) · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
backgroundTriple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis, and there are no targeted treatments available. TNBC patients are more likely to develop metastases and relapse than patients with other breast cancer subtypes. Lymph node metastasis is the first sign of metastatic spread. We aimed to characterize the mechanism of lymph node metastasis in TNBC to provide a new strategy for the treatment of TNBC.
methodsGene Expression Omnibus (GEO) TNBC database was utilized to screen for genes related to N staging. Screening the downstream target of Melanophilin (MLPH) in TNBC through RNA sequencing (RNA seq) analysis. Protein mass spectrometry was utilized to analyze the protein which interacts with MLPH, and RNA binding protein immunoprecipitation and quantitative real-time PCR (RIP qPCR) were utilized to verify the regulation of sphingosine kinase 1 (SPHK1) expression by MLPH through Non-POU domain-containing octamer-binding protein (NONO). Cell functional assays and in vivo models experiments further confirmed the effects of MLPH on proliferation and lymph node metastasis of TNBC through the SPHK1-S1P axis.
resultsMLPH is downregulated in TNBC and inhibits tumor growth and lymph node metastasis though the MLPH-NONO-SPHK1-S1P pathway. NONO was identified as an essential factor involved in SPHK1 mRNA splicing. MLPH interacts with NONO to inhibit SPHK1 mRNA splicing of SPHK1, which reduces the content of S1P, thereby inhibiting growth and lymph node metastasis in TNBC.
conclusionsThis study preliminarily elucidated a mechanism underlying lymph node metastasis in TNBC and identified the role of the MLPH-NONO-SPHK1-S1P axis in regulating proliferation and lymph node metastasis in TNBC. These findings may help design strategies for predicting and treating metastasis in TNBC.
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