ArticleCell death discovery2021
LHPP suppresses colorectal cancer cell migration and invasion in vitro and in vivo by inhibiting Smad3 phosphorylation in the TGF-β pathway.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Microbial metabolite Enterobactin impairs mitochondrial respiration and alleviates colitis.Gut microbes · 2026Article
- Gut microbiome derived folate metabolite suppresses colorectal cancer progression.bioRxiv : the preprint server for biology · 2026Article
- Advances in signaling pathway networks involving LHPP in various diseases.Molecular and cellular biochemistry · 2026Review
- LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TCF7 functions as a prognostic biomarker in bladder cancer by strengthening EMT and stemness associated with TGF-β/SMAD3 signaling.Molecular and cellular biochemistry · 2025Article
- PTMFusionNet: A Deep Learning Approach for Predicting Disease Related Post-translational Modification and Classifying Disease Subtypes.Molecular & cellular proteomics : MCP · 2025Article
- Targeting LHPP in neoadjuvant chemotherapy resistance of gastric cancer: insights from single-cell and multi-omics data on tumor immune microenvironment and stemness characteristics.Cell death & disease · 2025Article
- LHPP-P38 MAPK/ERK-ETS1 Axis Negative Feedback Signaling Restrains Progression in Breast Cancer.Cancer science · 2025Article
- Selective anti-cancer effects of cannabidiol and Δ9-tetrahydrocannabinol via PI3K/AKT/mTOR inhibition and PTEN restoration in ovarian cancer cells.Frontiers in pharmacology · 2025Article
- Deciphering STAT3's negative regulation of LHPP in ESCC progression through single-cell transcriptomics analysis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Histidine phosphatase-ferroptosis crosstalk modulation for efficient hepatocellular carcinoma treatment.Journal of nanobiotechnology · 2024Article
- Phosphatase LHPP confers prostate cancer ferroptosis activation by modulating the AKT-SKP2-ACSL4 pathway.Cell death & disease · 2024Article
- Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024Review
- Oncolytic adenovirus encoding LHPP exerts potent antitumor effect in lung cancer.Scientific reports · 2024Article
- Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance.Cellular and molecular life sciences : CMLS · 2024Review
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- Review
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- Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids.Environmental science & technology · 2023Article
- Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The roles of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) in tumorigenesis have been recently proven in hepatocellular carcinoma (HCC), cervical, pancreatic, bladder, and thyroid cancers. Previous research demonstrated that LHPP repressed cell proliferation and growth by inactivating the phosphatidylinositol 3-kinase/AKT signaling pathway in vitro and in vivo. However, the functions and potential mechanisms of LHPP as a tumor suppressor in colorectal cancer (CRC) metastasis are still unknown. Consequently, the Transwell assay and xenograft nude model showed that LHPP inhibited migration and invasion of CRC cells in vitro and in vivo, respectively. The expression of total and nuclear epithelial-to-mesenchymal transition (EMT)-related proteins were significantly reduced after LHPP upregulation. Human Gene Expression Array and IPA (Ingenuity Pathway Analysis) commercial software were applied to identify differentially expressed genes (DEGs) and potential cell signaling pathways. A total of 330 different genes were observed, including 177 upregulated genes and 153 downregulated genes. Bioinformatics analysis suggested that the transforming growth factor-β (TGF-β) signaling pathway was highly inactivated in this study. Then, Smad3 phosphorylation was apparently decreased, whereas Smad7 expression was markedly enhanced after upregulating LHPP expression. These results were proven once again after TGF-β1 stimulation. Furthermore, a specific inhibitor of Smad3 phosphorylation (SIS3) was applied to verify that LHPP repressed EMT of cancer cells by attenuating TGF-β/Smad signaling. The results suggested that suppression of the TGF-β/Smad signaling pathway by LHPP overexpression could be abolished by SIS3.
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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 OpenQuestion graph.