Phospholipase D (PLD) activity has been implicated in several aspects of cell physiology including vesicle transport, signal transduction, cell proliferation, cytoskeletal structure, and oncogenic transformation. Two PLD isoforms (PLD1 and PLD2) have been identified and characterized. We have expressed both wild-type and catalytically inactive forms of PLD1 and PLD2 in 3Y1 rat fibroblasts and in 3Y1 cells transformed by v-Src, a tyrosine kinase that elevates PLD activity. The v-Src-transformed 3Y1 cells have small, but distinct cell protrusions, implicated in cell migration and metastasis. We report here that elevated expression of PLD2 substantially increased the length of the cell protrusions and that a catalytically inactive PLD2 mutant abolished the cell protrusions. The extended protrusions in the PLD2-overexpressing cells were dependent upon microtubule assembly. These data suggest a role for PLD2 in the v-Src-mediated formation of cell protrusions that may be critical for the invasive properties of v-Src-transformed cells.
v-Src increases diacylglycerol levels via a type D phospholipase-mediated hydrolysis of phosphatidylcholine.
Lysophosphatidic acid activation of phosphatidylcholine-hydrolysing phospholipase D and actin polymerization by a pertussis toxin-sensitive mechanism
v-Src activates a unique phospholipase D activity that can be distinguished from the phospholipase D activity activated by phorbol esters
Induction of in vitro tumor cell invasion of cellular monolayers by lysophosphatidic acid or phospholipase D
A phospholipase D and protein kinase C inhibitor blocks the spreading of murine mammary adenocarcinoma cells altering f-actin and beta1-integrin point contact distribution
Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization
Suppression of matrix metalloproteinase-2-mediated cell invasion in U87MG, human glioma cells by anti-microtubule agent: in vitro study
Secretion of urokinase and metalloproteinase-9 induced by staurosporine is dependent on a tyrosine kinase pathway in mammary tumor cells
Phospholipase D mediates matrix metalloproteinase-9 secretion in phorbol ester-stimulated human fibrosarcoma cells.
RalA requirement for v-Src- and v-Ras-induced tumorigenicity and overproduction of urokinase-type plasminogen activator: involvement of metalloproteases
Antagonistic effects of protein kinase C alpha and delta on both transformation and phospholipase D activity mediated by the epidermal growth factor receptor.
Phospholipase D and RalA cooperate with the epidermal growth factor receptor to transform 3Y1 rat fibroblasts.
RalA mediates v-Src, v-Ras, and v-Raf regulation of CD44 and fibronectin expression in NIH3T3 fibroblasts
Activation of ARF6 by ARNO stimulates epithelial cell migration through downstream activation of both Rac1 and phospholipase D
Signal pathways which promote invasion and metastasis: critical and distinct contributions of extracellular signal-regulated kinase and Ral-specific guanine exchange factor pathways.
Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model
Phospholipase D activity regulates integrin-mediated cell spreading and migration by inducing GTP-Rac translocation to the plasma membrane.
Targeting phospholipase D with small-molecule inhibitors as a potential therapeutic approach for cancer metastasis.
Serum deprivation confers the MDA-MB-231 breast cancer line with an EGFR/JAK3/PLD2 system that maximizes cancer cell invasion
Paxillin phosphorylation and complexing with Erk and FAK are regulated by PLD activity in MDA-MB-231 cells.
Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells
v-Src accelerates spontaneous motility via phosphoinositide 3-kinase, phospholipase C and phospholipase D, but abrogates chemotaxis in Rat-1 and MDCK cells
The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF).
Cell Migration in Cancer and Metastasis
Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.
Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.