Role of phosphoinositide metabolism in cell polarity format

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We first examined the roles of PIP_2 in the invadopodia formation of human breast cancer cells. PIP2 accumulated at invadopodia, and injection of antibody against PIP2 blocked invadopodia formation. In addition, knockdown (KD) of PIP5KIa inhibited invadopodia formation. These results indicate that localized production of PIP2 by PIP5KIa is required for invadopodia formation and ECM degradation by human breast cancer cells.On the other hand, we also found that the skin of PLCd1KO mice displays typical inflammatory phenotypes, including leukocyte infiltration, and expression of pro-inflammatory cytokines. We also detected that PLCd1KO mice had significantly elevated peripheral blood leukocytes compared to wild-type mice. These results indicate that lack of PLCd1 induces skin inflammation and systemic neutrophilia.