ArticleCancer cell international2017
Hypoxia and TGF-β1 induced PLOD2 expression improve the migration and invasion of cervical cancer cells by promoting epithelial-to-mesenchymal transition (EMT) and focal adhesion formation.
Article in Cancer cell international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58 citing papers in PubMed, 119 citations in OpenAlex.
- Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients.PLoS biology · 2026Article
- Targeting PLOD2 induces epithelioid differentiation and improves therapeutic response in sarcomatoid renal cell carcinoma.Journal of advanced research · 2026Article
- Exploring mechanisms of scar-free skin wound healing in adult zebrafish in comparison to mouse.PLoS genetics · 2026Article
- Intermittent parathyroid hormone employs autonomous and non-autonomous mechanisms to drive osteogenesis from Ebf3-expressing skeletal progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- PLOD2 promotes proliferation, migration and invasion of colorectal cancer cells via PI3K-AKT-GSK3β signaling pathway.Scientific reports · 2026Article
- Mucin 5ac modulates cancer-associated fibroblast heterogeneity through epigenetic reprogramming of precursor cells.American journal of physiology. Cell physiology · 2026Article
- Lifting regenerative barriers promotes epithelial cell fate plasticity supporting lineage conversion.Nature communications · 2025Article
- Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules.ACS central science · 2025Article
- Mimicking Gastric Cancer Collagen Reorganization with Decellularized ECM-Based Scaffolds.Biology · 2025Review
- Construction and validation of a cell-in-cell related prognostic signature for hepatocellular carcinoma.Discover oncology · 2025Article
- miR-216 Is a Key Regulator and Potential Marker in Human Cancers.Advanced biomedical research · 2025Review
- MK2-mediated AKT/MYC signaling activation promotes epithelial-mesenchymal transition in lung adenocarcinoma.Frontiers in genetics · 2025Article
- Article
- The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen.International journal of molecular sciences · 2024Review
- Sarcoma Cells Secrete Hypoxia-Modified Collagen VI to Weaken the Lung Endothelial Barrier and Promote Metastasis.Cancer research · 2024Article
- METTL3 facilitates renal cell carcinoma progression by PLOD2 mCell death & disease · 2024Article
- Targeting PLOD2 suppresses invasion and metastatic potential in radiorecurrent prostate cancer.BJC reports · 2024Article
- Dysregulation of PLOD2 Promotes Tumor Metastasis and Invasion in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Article
- Synthesis and Antitumor Activity of Brominated-Ormeloxifene (Br-ORM) against Cervical Cancer.ACS omega · 2023Article
- The PLOD2/succinate axis regulates the epithelial-mesenchymal plasticity and cancer cell stemness.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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5 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundIntra-tumoral hypoxia and increases in extracellular level of transforming growth factor β1 (TGF-β1), which are common findings in cancer, are associated with an increased risk of metastasis and mortality. Moreover, metastasis is the leading cause of death of patients with cervical cancer. PLOD2 is an intracellular enzyme required for the biogenesis of collagen and its expression can be induced by hypoxia and TGF-β1. Specifically, PLOD2 is up-regulated in several types of cancer, including cervical cancer, and is associated with cancer metastasis. Thus, in this research, we aimed to investigate the role of PLOD2 in the motility of cervical cancer cells and to show the molecular mechanism underlying this effect.
methodssiRNA was used to knockdown PLOD2 in the cervical cancer cell lines HeLa and SiHa. The ability of cells to migrate and invade, their adhesion to type I collagen, and their capacity for epithelial-to-mesenchymal transition (ΕΜΤ) and focal adhesion formation were analyzed. Gene expression changes were validated by qRT-PCR, Western blotting and Immunocytochemistry. The morphological status of cells was examined using phalloidin staining. Differences in PLOD2 expression among patients with cervical cancer were identified by referring to public databases, including Oncomine and TCGA.
resultsHypoxia and TGF-β1 enhanced the expression of PLOD2 in HeLa and SiHa cells, and knockdown of PLOD2 inhibited cell motility and EMT. Moreover, the depletion of PLOD2 attenuated hypoxia-mediated cell migration and invasion and inhibited TGF-β1-induced phenotypic EMT-like changes by preventing β-catenin from entering the nucleus. In addition, PLOD2 depletion decreased cell adhesion to extracellular collagen by inhibiting the formation of focal adhesions. Moreover, a database analysis showed that PLOD2 expression is associated with human cervical cancer progression.
conclusionsOverall, our results indicated that hypoxia- and TGF-β1-induced PLOD2 expression promotes the migratory, invasive and adhesive capacities of cervical cancer cells by participating in TGF-β1 induced EMT and the formation of focal adhesions.
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