ArticleMolecular medicine (Cambridge, Mass.)2020
The SP1-12LOX axis promotes chemoresistance and metastasis of ovarian cancer.
Article in Molecular medicine (Cambridge, Mass.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- COL1A1-induced LOXL2 promotes ovarian cancer metastasis via a feedback loop upon inhibiting EGFR lysosomal degradation.Experimental & molecular medicine · 2026Article
- Understanding the immunomodulatory mechanisms for natural products that overcome tumor chemoresistance to platinum-based cancer drugs and other treatments.Frontiers in pharmacology · 2026Review
- 5-HEPE Ameliorates Aging of Duck Ovarian Granulosa Cells by Targeting FOXM1 and Suppressing Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- HMGA1 drives EMT in obliterative bronchiolitis through epigenetic regulation of chromatin accessibility in pulmonary epithelial cells.Clinical epigenetics · 2025Article
- Synergistic overcoming of cisplatin resistance in ovarian cancer by combined Astragalus Membranaceus and cisplatin treatment: network pharmacology and experimental validation.BMC complementary medicine and therapies · 2025Article
- Transcription factor SP1 drives the malignant progression of oral squamous cell carcinoma and M2 macrophage polarization through transcription activation-mediated upregulation CLEC7A.Cytotechnology · 2025Article
- MEOX2 mediates cisplatin resistance in ovarian cancer via E2F target and DNA repair pathways.Journal of ovarian research · 2025Article
- Combinatorial functionomics identifies HDAC6-dependent molecular vulnerability of radioresistant head and neck cancer.Experimental hematology & oncology · 2025Article
- Organoid models of ovarian cancer: resolving immune mechanisms of metabolic reprogramming and drug resistance.Frontiers in immunology · 2025Review
- Decoding gene regulatory circuitry underlying TNBC chemoresistance reveals biomarkers for therapy response and therapeutic targets.NPJ precision oncology · 2024Article
- Identification of Copper Homeostasis-Related Gene Signature for Predicting Prognosis in Patients with Epithelial Ovarian Cancer.Cancer informatics · 2024Article
- The deregulation of arachidonic acid metabolism in ovarian cancer.Frontiers in oncology · 2024Review
- Baicalein Induces GMolecules (Basel, Switzerland) · 2023Article
- Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer.Frontiers in oncology · 2023Review
- Detection of Ferroptosis by Immunohistochemistry and Immunofluorescence.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Association between abnormal lipid metabolism and tumor.Frontiers in endocrinology · 2023Review
- A diagnostic miRNA panel to detect recurrence of ovarian cancer through artificial intelligence approaches.Journal of cancer research and clinical oncology · 2023Article
- SP1-induced lncRNA MCF2L-AS1 promotes cisplatin resistance in ovarian cancer by regulating IGF2BP1/IGF2/MEK/ERK axis.Journal of gynecologic oncology · 2022Article
- Curcumol repressed cell proliferation and angiogenesisFrontiers in pharmacology · 2022Article
- Progress and challenges of multidrug resistance proteins in diseases.American journal of cancer research · 2022Review
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOvarian cancer is the most lethal gynecologic cancer. Chemoresistance, especially platinum-resistance, is closely related to metastasis of ovarian cancer, however, the molecular basis by which links chemoresistance and metastasis remains vague. Disordered arachidonic acid (AA) metabolism has been shown to play an important role in the advanced ovarian cancer. This study aimed to explore the underlying mechanism involving eicosanoid metabolism that controlling chemoresistance and metastasis of ovarian cancer.
methodsCisplatin (DDP)-resistant SKOV3 (SKOV3-R) cells were constantly induced. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was performed to determine the AA metabolism in SKOV3 and SKOV3-R cells. Half maximal inhibitory concentration (IC50) and percentage of cell viability were tested using cell counting kit 8 (CCK-8). Realtime quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to evaluate indicated genes and proteins respectively. Bioinformatic analysis and chromatin immunoprecipitation (ChIP) were performed to predict and identify the co-transcription factor of interest genes. Tumor growth and metastasis in the liver were assessed with nude mice by subcutaneously injection of SKOV3-R cells.
resultsSKOV3-R cells expressed higher multidrug resistance-associated proteins (MRPs) MRP1 and MRP4. They showed enhanced metastatic ability and produced increased AA-derived eicosanoids. Mechanistically, MRPs, epithelial mesenchymal transition (EMT) markers Snail and Slug, as well as key enzymes involved in AA-metabolism including 12-lipoxygenase (12LOX) were transcribed by the mutual transcription factor SP1 which was consistently upregulated in SKOV3-R cells. Inhibition of SP1 or 12LOX sensitized SKOV3-R cells to DDP and impaired metastasis in vitro and in vivo.
conclusionOur results reveal that SP1-12LOX axis signaling plays a key role in DDP-resistance and metastasis, which provide a new therapeutic target for ovarian cancer.
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