Table 1 Impact of four potential PI(4,5)P2 deregulation patterns in cancer cells on Cancer Progression and Metastasis
From: Plasma membrane and nuclear phosphatidylinositol 4,5-bisphosphate signalling in cancer
High cytosol levels– High nuclear levels | Low cytosol levels– High nuclear levels: |
|---|---|
♦ Enhanced cytoplasmic signalling (promoted PI3K/Akt signalling pathway) > increased cell survival, proliferation, angiogenesis, invasiveness. ♦ Dysregulation of actin polymerisation and cytoskeletal remodelling > enhanced cytoskeletal dynamics, cell migration and adhesion. ♦ Promotion of Factin assembly > enhanced migration. ♦ Enhanced invadopodia dynamics (formation and stability) -> ECM degradation. ♦ Enhanced/alternate transcription of genes involved in DNA damage repair, cell proliferation -> promotion of genome stability and cancer cell survival. ♦ Activation of genes involved in cytoskeletal remodelling metastasis | ♦ Attenuated PI3K/Akt signalling > impaired cell migration and invasion. ♦ Altered cytoskeletal remodelling > limited dynamics, reduced actin polymerisation, decreased assembly of Factin. ♦ Accumulation of free Gactin molecules > possibility of translocation to the nucleus. ♦ Impaired invadopodia formation. ♦ Activation of signalling pathways involved in the regulation of transcription and DNA damage repair. ♦ Activation of genes involved in cytoskeletal remodelling > metastasis. |
High cytosol levels– Low nuclear levels | Low cytosol levels– Low nuclear levels |
♦ Enhanced cytoplasmic signalling (promoted PI3K/Akt signalling pathway) > increased cell survival, proliferation, angiogenesis, invasiveness. ♦ Dysregulation of actin polymerisation and cytoskeletal remodelling > enhanced cytoskeletal dynamics, cell migration and adhesion. ♦ Promotion of Factin assembly > enhanced migration. ♦ Enhanced invadopodia dynamics (formation and stability) > ECM degradation ♦ Limited/ Attenuated regulation of transcription > altered gene expression profiles. ♦ Decrease nuclear actin levels > impaired chromatin organisation. ♦ Defective DNA repair mechanism > genome instability. | ♦ Attenuated PI3K/Akt signalling -> decreased proliferation, cell survival and invasiveness. ♦ Limited cytoskeletal dynamics > reduced motility ♦ Attenuated regulation of transcription -> altered gene expression profiles, decreased invasive potential. ♦ Impaired gene expression. ♦ Decrease nuclear actin levels -> impaired chromatin organisation. |