ArticleCancer cell international2021
Alkaline phosphatase downregulation promotes lung adenocarcinoma metastasis via the c-Myc/RhoA axis.
Article in Cancer cell international, 2021. 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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16 citing papers in PubMed, 30 citations in OpenAlex.
- Coronary Microvascular Dysfunction: Epidemiology, Pathophysiology, Diagnosis, and Treatment.MedComm · 2026Review
- Circadian-immune-related gene signature for lung squamous cell carcinoma: machine learning and multi-omics analysis.Translational cancer research · 2026Article
- Alkaline phosphatase (ALPL) as a diagnostic and prognostic biomarker linked to immune response in thyroid cancer.Gland surgery · 2025Article
- Evaluation of serum alkaline phosphatase and lactate dehydrogenase as predictive biomarkers for the prognosis of male breast cancer.Scientific reports · 2025Article
- Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Therapeutic and prognostic effect of disulfidptosis-related genes in lung adenocarcinoma.Heliyon · 2024Article
- Elucidating the role of liver enzymes as markers and regulators in ovarian cancer: a synergistic approach using Mendelian randomization, single-cell analysis, and clinical evidence.Human genomics · 2024Article
- Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma.Current medical science · 2024Article
- Do alkaline phosphatases have great potential in the diagnosis, prognosis, and treatment of tumors?Translational cancer research · 2023Review
- Article
- Identification of RAC1 in promoting brain metastasis of lung adenocarcinoma using single-cell transcriptome sequencing.Cell death & disease · 2023Article
- Enzyme-instructed morphology transformation of mitochondria-targeting peptide for the selective eradication of osteosarcoma.RSC chemical biology · 2022Article
- Inhibitory role of puerarin on the A549 lung cancer cell line.Translational cancer research · 2022Article
- The VJournal of endocrinological investigation · 2022Article
- Biomineralization associated alkaline phosphatase as a potential marker of bone metastasis in the patients with invasive breast cancer.Saudi journal of biological sciences · 2022Article
- TRIB2 regulates the expression of miR‑33a‑5p through the ERK/c‑Fos pathway to affect the imatinib resistance of chronic myeloid leukemia cells.International journal of oncology · 2022Article
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12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundLung adenocarcinoma (LUAD) metastasis significantly reduces patient survival; hence inhibiting the metastatic ability of lung cancer cells will greatly prolong patient survival. Alkaline phosphatase (ALPL), a homodimeric cell surface phosphohydrolase, is reported to play a controversial role in prostate cancer and ovarian cancer cell migration; however, the function of ALPL in LUAD and the related mechanisms remain unclear.
methodsTCGA database was used to analysis the expression of ALPL, and further verification was performed in a cohort of 36 LUAD samples by qPCR and western blot. Soft-agar assay, transwell assay and lung metastasis assay were employed to detect the function of ALPL in LUAD progression. The qPCR, luciferase promoter reporter assay and western blot were used to clarify the molecular mechanisms of ALPL in promoting metastasis in LUAD.
resultsALPL was downregulated in LUAD, and the disease-free survival rate of patients with low ALPL was significantly reduced. Further studies showed that overexpression of ALPL in LUAD cell lines did not significantly affect cell proliferation, but it did significantly attenuate lung metastasis in a mouse model. ALPL downregulation in LUAD led to a decrease in the amount of phosphorylated (p)-ERK. Because p-ERK promotes the classical c-Myc degradation pathway, the decrease in p-ERK led to the accumulation of c-Myc and therefore to an increase in RhoA transcription, which enhanced LUAD cell metastasis.
conclusionALPL specially inhibits the metastasis of LUAD cells by affecting the p-ERK/c-Myc/RhoA axis, providing a theoretical basis for the targeted therapy of clinical LUAD.
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