ArticleCancer science2010
Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Ialpha are required for invadopodia formation in human breast cancer cells.
Article in Cancer science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Implicates of PIP5K1α in asthma-related biological processes: insights into mechanisms and therapeutic potential.Journal of translational medicine · 2025Review
- A Novel Interaction between Chemokine and Phosphoinositide Signaling in Metastatic Prostate Cancer.Medical research archives · 2023Article
- Characterization of a PIP Binding Site in the N-Terminal Domain of V-ATPase a4 and Its Role in Plasma Membrane Association.International journal of molecular sciences · 2023Article
- Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer.Frontiers in oncology · 2023Review
- PI(4,5)P2: signaling the plasma membrane.The Biochemical journal · 2022Article
- Human β-Defensin 2 (HBD-2) Displays Oncolytic Activity but Does Not Affect Tumour Cell Migration.Biomolecules · 2022Article
- PI(3,4)PProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Hedgehog signaling and Tre1 regulate actin dynamics through PI(4,5)PCell reports · 2021Article
- A multiscale biophysical model for the recruitment of actin nucleating proteins at the membrane interface.Soft matter · 2020Article
- K-Ras G-domain binding with signaling lipid phosphatidylinositol (4,5)-phosphate (PIP2): membrane association, protein orientation, and function.The Journal of biological chemistry · 2019Article
- The role of PIP5K1α/pAKT and targeted inhibition of growth of subtypes of breast cancer using PIP5K1α inhibitor.Oncogene · 2019Article
- NEDD4-induced degradative ubiquitination of phosphatidylinositol 4-phosphate 5-kinase α and its implication in breast cancer cell proliferation.Journal of cellular and molecular medicine · 2018Article
- The store-operated calcium channels in cancer metastasis: from cell migration, invasion to metastatic colonization.Frontiers in bioscience (Landmark edition) · 2018Article
- A new front in cell invasion: The invadopodial membrane.European journal of cell biology · 2016Review
- Human β-defensin 3 contains an oncolytic motif that binds PI(4,5)P2 to mediate tumour cell permeabilisation.Oncotarget · 2016Article
- The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based WAVE2 complex.Cell communication and signaling : CCS · 2015Article
- The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Myosin 1e is a component of the invadosome core that contributes to regulation of invadosome dynamics.Experimental cell research · 2014Article
- Podosomes of dendritic cells facilitate antigen sampling.Journal of cell science · 2014Article
- Amplification of Chromosome 1q Genes Encoding the Phosphoinositide Signalling Enzymes PI4KB, AKT3, PIP5K1A and PI3KC2B in Breast Cancer.Journal of Cancer · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Invadopodia are ventral cell protrusions formed in invasive cancer cells. Because invadopodia have extracellular matrix (ECM) degradation activity, they are thought to function in cancer invasion. In this study, we examined the roles of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and PI(4,5)P(2)-producing enzymes in invadopodia formation in MDA-MB-231 human breast cancer cells. Immunofluorescence analysis showed that PI(4,5)P(2) accumulates at invadopodia on the ventral cell surface. Injection of an anti-PI(4,5)P(2) antibody inhibited invadopodia formation along with gelatin degradation activity. Sequestering of PI(4,5)P(2) by overexpression of the phospholipase C (PLC) delta1-pleckstrin homology (PH) domain, a specific probe for PI(4,5)P(2), also blocked invadopodia formation, while a mutated PLCdelta1-PH domain that lacks PI(4,5)P(2)-binding activity had no effect. Cellular PI(4,5)P(2) production is mainly mediated by type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5KI) family proteins, which include PIP5KIalpha, Ibeta, and Igamma. Real-time quantitative PCR analysis showed that PIP5KIalpha is a dominant isoform expressed in MDA-MB-231 cells. Knockdown of PIP5KIalpha by small-interfering RNA (siRNA) inhibited invadopodia formation and gelatin degradation. Immunofluorescence analysis revealed that endogenous PIP5KIalpha protein localizes at invadopodia, which is corroborated by the observation that exogenously expressed green fluorescent protein (GFP)-fused PIP5KIalpha protein also accumulates at gelatin degradation sites. These results indicate that localized production of PI(4,5)P(2) by PIP5KIalpha is required for invadopodia formation and ECM degradation by human breast cancer cells.
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