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Prof. Sima Lev - Lipid transfer proteins in cancer biology & metastasis
1. Prof. Sima Lev,
Molecular Cell Biology Department
Weizmann Institute of Science, Rehovot, Israel
Lipid dynamics and membrane contact sites
FEBS 2018, 31 August- 7 September, Spetses, Greece
Lipid transfer proteins in cancer biology & metastasis
2. PIns signaling & Cancer
Nir2 in EMT and cancer Metastasis
Other LTPs and cancer progression & metastasis
Lipid transfer proteins in cancer biology & metastasis
Nir2 regulates PIns-associated signaling pathways
MAPK, PI3K/AKT
LTPs in breast cancer; bioinformatic analysis
Open questions & further approaches
8. Wild type Nir2, but not its mutants, restores PI(4,5)P2 levels at
the PM of Nir2-depleted cells
Kim. et al, EMBO Reports 2013
Nir2 is an upstream regulator of key phosphoinositide pathways in
mammalian cells: the PI3K/AKT and MAPK pathways
9. SUMMARY
LTPs transfer lipids according to the lipid composition of their target membrane
Mechanistic Insight underlying lipid transfer by LTPs
LTPs coordinate the level of different lipid species at specific membrane domains
Cytokinesis, cell growth, migration, EMT
Physiological roles
Neurodegeneration, cancer & metastasis
Pathological implications
Regulation?
Post translation modifications?
Interacting proteins?
Targeting?
Editor's Notes
only a small subset of PH domains in the human genome are thought to bind PIP3 with high affinity and specificity (10–20% out of 290 PH domains have been shown to robustly bind phosphoi-nositides, with some of these robustly binding PI-3,4-P2 or PI-4,5-P2 but not PIP3) [9,10]. Of the PH domain-containing proteins that do bind PIP3, the serine/threo-nine AGC-family protein kinase AKT has received the greatest attention, especially for its multi-faceted roles in promoting glucose metabolism and cancer