Fig 1: IBSP overexpression promoted CRC cell proliferation, invasion as well as migration via Fyn/β‐catenin pathway. *p < 0.05, **p < 0.01, ***p < 0.001,**** p < 0.0001, ns: nonsignificant. (A) Upregulation of IBSP mRNA in CRC cells. (B) IBSP overexpression promoted cell proliferation of CRC cells. (C) IBSP overexpression significantly increased the number of cell colonies. (D) IBSP overexpression promoted invasion and migration of CRC cells. (E) IBSP overexpression increased the protein level of PCNA, Bcl2, Cyclin D1, Cdk4, MMP2, MMP9, N‐cadherin, Vimentin, Fyn, p‐Fyn, and p‐β‐catenin and decreased the expression of Bax and E‐cadherin
Fig 2: The mechanisms of IBSP function in CRC. *p < 0.05; **p < 0.01; ns: nonsignificant. (A) The LYN mRNA expression following IBSP downregulation. (B) The FYN mRNA expression following IBSP downregulation. (C) The LCK mRNA expression following IBSP downregulation. (D) Protein level of Fyn, p‐Fyn, and p‐β‐catenin decreased after transfection of IBSP‐siRNA, while β‐catenin showed no significant variation. (E) The expression of IBSP was significantly positively correlated with the expression of Fyn and β‐catenin
Fig 3: Bimoclomol mediated improvements in cerebellar weight and myelination are blocked by saracatinib co-treatment. Representative Western blots & relative expression of a) cerebellar MBP (n = 4/group), b) cerebellar Fyn (n = 4/group) and c) cerebellar wet weights (Npc1+/+ + vehicle: n = 6; Npc1+/+ + saracatinib: n = 6; Npc1+/+ + bimoclomol (Bim): n = 5; Npc1+/+ + bim/sara: n = 5; Npc1−/− + vehicle: n = 6; Npc1−/− + saracatinib: n = 5; Npc1−/− + bimoclomol (Bim): n = 5; Npc1−/− + bim/sara: n = 6) in Npc1+/+ or Npc1−/− mice at P35 following treatment with vehicle, 10 mg/kg/day of either saracatinib or bimoclomol, or a combination of bimoclomol/saracatinib (bim/sara). Data are presented as mean + SD. Effects of treatments were analysed using a two-way ANOVA on log-transformed values. Multiplicity was adjusted using Dunnett's method (n = 3 comparisons; ∗p< 0.05, ∗∗p< 0.01, ∗∗∗p< 0.001, ∗∗∗∗p < 0.0001).
Fig 4: Treatment with rhHSP70 or bimoclomol increases the ratio of active-to-inactive phosphorylated forms of Fyn kinase in the cerebellum of Npc1−/− mice. Representative Western blots of total Fyn and its phosphorylated active (pY418) and inactive (pY531) forms following immunoprecipitation of Fyn kinase in a) cerebellar samples from Npc1+/+ comparators or Npc1−/− mice following treatment with PBS (vehicle), rhHSP70, or bimoclomol (bim) at P35. b) Quantification of the relative levels of the phosphorylated active and inactive forms of Fyn kinase as well as the ratio of pY418:pY531. Data are presented as the mean + SD of three independent experiments using n = 3 mice per treatment group. Effects of treatments were analysed using a one-way ANOVA on log-transformed values and multiplicity was adjusted using Dunnett's method (n = 2 comparisons; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001).
Supplier Page from Abcam for Anti-Fyn (phospho Y530) + Yes (phospho Y537) antibody [EPR13512]