ArticleScientific reports2020
MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Albiflorin-Mediated MAP2K1 Targeting and HIF-1 Signaling Inhibition Contribute to the Therapeutic Efficacy in Hyperuricemia-Associated Cognitive Impairment.Human mutation · 2026Article
- Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT).Scientific reports · 2025Article
- Hemin Promotes Higher Effectiveness of Aminolevulinic-Photodynamic Therapy (ALA-PDT) in A549 Lung Cancer Cell Line by Interrupting ABCG2 Expression.Medical sciences (Basel, Switzerland) · 2024Article
- Systematic Review of Photodynamic Therapy in Gliomas.Cancers · 2023Review
- Construction and experimental validation of a macrophage cell senescence-related gene signature to evaluate the prognosis, immunotherapeutic sensitivity, and chemotherapy response in bladder cancer.Functional & integrative genomics · 2023Article
- Interstitial Photodynamic Therapy of Glioblastomas: A Long-Term Follow-up Analysis of Survival and Volumetric MRI Data.Cancers · 2023Article
- Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023Review
- Inflammatory cell death induced by 5-aminolevulinic acid-photodynamic therapy initiates anticancer immunity.Frontiers in oncology · 2023Article
- High quantum efficiency ruthenium coordination complex photosensitizer for improved radiation-activated Photodynamic Therapy.Frontiers in oncology · 2023Article
- Glioblastoma-derived extracellular vesicle subpopulations following 5-aminolevulinic acid treatment bear diagnostic implications.Journal of extracellular vesicles · 2022Article
- Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy.Nature communications · 2022Article
- Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions.International journal of molecular sciences · 2022Article
- Small-molecule inhibitors of ferrochelatase are antiangiogenic agents.Cell chemical biology · 2022Article
- Minimizing adverse effects of Cerenkov radiation induced photodynamic therapy with transformable photosensitizer-loaded nanovesicles.Journal of nanobiotechnology · 2022Article
- Detection of Canine Urothelial Carcinoma Cells in Urine Using 5-Aminolevulinic Acid.Animals : an open access journal from MDPI · 2022Article
- Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis.Open life sciences · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) and ferrochelatase (FECH)-catalysed PpIX conversion to haem. Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1α expression was reduced when RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1α is a downstream element of MEK. HIF-1α inhibition decreased FECH activity and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1α in the regulation of PpIX accumulation in human cancer cell lines. These results demonstrate that the RSK-ABCB1 and HIF-1α-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.
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