ArticleCancer research2019
A Direct Podocalyxin-Dynamin-2 Interaction Regulates Cytoskeletal Dynamics to Promote Migration and Metastasis in Pancreatic Cancer Cells.
Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- PODXL2 Promotes Cholangiocarcinoma Progression via Interactions with Ezrin and Activation of the MAPK/ERK1/2 and PI3K/AKT Signaling Pathways.Digestive diseases and sciences · 2026Article
- Intracellular sclerostin promotes tumor progression and metastasis as a potential therapeutic target in triple-negative breast cancer.Cell reports. Medicine · 2026Article
- High-fat diet-responsive DNM1 promotes hepatocellular carcinoma progression and predicts poor prognosis in viral-associated patients.American journal of cancer research · 2026Article
- Cytoplasmic anillin and Ect2 promote RhoA/myosin II-dependent confined migration and invasion.Nature materials · 2025Article
- Nuclear Expression of Dynamin 2 Is Associated With Tumor Aggressiveness in Bladder Cancer Patients: A Bioinformatics and Experimental Approach.Cancer reports (Hoboken, N.J.) · 2024Article
- Tumor endothelium-derived PODXL correlates with immunosuppressive microenvironment and poor prognosis in cervical cancer patients receiving radiotherapy or chemoradiotherapy.Biomarker research · 2024Article
- Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells.Journal of translational medicine · 2024Article
- PKCα Induced the Generation of Extracellular Vesicles in Activated Platelets to Promote Breast Cancer Metastasis.International journal of biological sciences · 2024Article
- Cancer-specific apoptosis induction in canine lymphoma cell lines by the endocytosis inhibitor dynasore.The Journal of veterinary medical science · 2023Article
- Metronomic Administration of Topotecan Alone and in Combination with Docetaxel Inhibits Epithelial-mesenchymal Transition in Aggressive Variant Prostate Cancers.Cancer research communications · 2023Article
- Rapid cancer cell perineural invasion utilizes amoeboid migration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Cell Biology of Metastatic Invasion in Pancreatic Cancer: Updates and Mechanistic Insights.Cancers · 2023Review
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- Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function.Science advances · 2023Article
- Article
- Dynamic regulation of KIF15 phosphorylation and acetylation promotes focal adhesions disassembly in pancreatic cancer.Cell death & disease · 2022Article
- Polarized NHE1 and SWELL1 regulate migration direction, efficiency and metastasis.Nature communications · 2022Article
- Development of versatile allele-specific siRNAs able to silence all the dominant dynamin 2 mutations.Molecular therapy. Nucleic acids · 2022Article
- Giant obscurin regulates migration and metastasis via RhoA-dependent cytoskeletal remodeling in pancreatic cancer.Cancer letters · 2022Article
- Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The sialoglycoprotein podocalyxin is absent in normal pancreas but is overexpressed in pancreatic cancer and is associated with poor clinical outcome. Here, we investigate the role of podocalyxin in migration and metastasis of pancreatic adenocarcinomas using SW1990 and Pa03c as cell models. Although ezrin is regarded as a cytoplasmic binding partner of podocalyxin that regulates actin polymerization via Rac1 or RhoA, we did not detect podocalyxin-ezrin association in pancreatic cancer cells. Moreover, depletion of podocalyxin did not alter actin dynamics or modulate Rac1 and RhoA activities in pancreatic cancer cells. Using mass spectrometry, bioinformatics analysis, coimmunoprecipitation, and pull-down assays, we discovered a novel, direct binding interaction between the cytoplasmic tail of podocalyxin and the large GTPase dynamin-2 at its GTPase, middle, and pleckstrin homology domains. This podocalyxin-dynamin-2 interaction regulated microtubule growth rate, which in turn modulated focal adhesion dynamics and ultimately promoted efficient pancreatic cancer cell migration via microtubule- and Src-dependent pathways. Depletion of podocalyxin in a hemispleen mouse model of pancreatic cancer diminished liver metastasis without altering primary tumor size. Collectively, these findings reveal a novel mechanism by which podocalyxin facilitates pancreatic cancer cell migration and metastasis. SIGNIFICANCE: These findings reveal that a novel interaction between podocalyxin and dynamin-2 promotes migration and metastasis of pancreatic cancer cells by regulating microtubule and focal adhesion dynamics.
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