https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 Loss of PI(4,5)P₂ 5-phosphatase A contributes to resistance of human melanoma cells to RAF/MEK inhibitors https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14384 V600E and by the MEK inhibitor U0126 in both BRAFV600E and wild-type BRAF melanoma cells. This was due to inhibition of PI3K/Akt, as co-introduction of an active form of Akt (myr-Akt) abolished the effect of overexpression of PIB5PA on apoptosis induced by PLX4720 or U0126. While overexpression of PIB5PA triggered activation of Bad and down-regulation of Mcl-1, knockdown of Bad or overexpression of Mcl-1 recapitulated, at least in part, the effect of myr-Akt, suggesting that regulation of Bad and Mcl-1 is involved in PIB5PA-mediated sensitization of melanoma cells to the inhibitors. The role of PIB5PA deficiency in BRAF inhibitor resistance was confirmed by knockdown of PIB5PA, which led to increased growth of BRAFV600E melanoma cells selected for resistance to PLX4720. Consistent with its role in vitro, overexpression of PIB5PA and the MEK inhibitor selumetinib cooperatively inhibited melanoma tumor growth in a xenograft model. Taken together, these results identify loss of PIB5PA as a novel resistance mechanism of melanoma to RAF/MEK inhibitors and suggest that restoration of PIB5PA may be a useful strategy to improve the therapeutic efficacy of the inhibitors in the treatment of melanoma.]]> Wed 11 Apr 2018 14:44:27 AEST ]]> The effects of PIB5PA on migration and invasion of human melanoma cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20768 P < 0.05), and reduced the expression levels of p-AKT, p-FAK, MMP-2, MMP-9, TIMP-1, TIMP-2, MMP-2/ TIMP-2 and MMP-9/TIMP-1 proteins (all P < 0.05). Conclusion: Over-expression of PIB5PA can inhibit the abilities of migration and invasion of human melanoma Mel-FH cells in vitro , which may be associated with inactivity of AKT and FAK, and down-regulation of the relative expression levels of MMP-2/TIMP-2 and MMP-9/TIMP-1.]]> Wed 11 Apr 2018 10:29:22 AEST ]]> Suppression of SHIP2 contributes to tumorigenesis and proliferation of gastric cancer cells via activation of Akt https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23968 Thu 17 Mar 2022 14:35:49 AEDT ]]> Autophagy-mediated HMGB1 release antagonizes apoptosis of gastric cancer cells induced by vincristine via transcriptional regulation of Mcl-1 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23419 Sat 24 Mar 2018 07:13:54 AEDT ]]>