Fig. 7: IP4 is a predictive biomarker of INPP5A dependence that is elevated in UM patients’ tumor samples.
From: INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas
a,b, Box plots showing IP4 levels displayed as µg per million cells in GNAQ/11WT cell lines, n = 8 and GNAQ/11Mut cell lines, n = 7 (a) or after treatment with DMSO or GNAQ/11 inhibitor (FR900359 10 nM) for 16 h in GNAQ/11WT cell lines, n = 6 and GNAQ/11Mut cell lines, n = 4 (b). c, Box plots showing IP4 levels displayed as µg g−1 of tumor tissue of 92.1 xenograft tumors. Mice were treated with vehicle or FR900359 (4 mg kg−1, i.v) for 24 h, n = 7 mice per group. d, Scatter-plot illustrating the correlation between cell viability upon INPP5A depletion and levels of IP4 in µg per million cells in GNAQ/11WT cell lines, n = 7 and GNAQ/11Mut cell lines, n = 6. e, Box plots of IP4 levels shown as µg g−1 of tumor tissue of PDX of GNAQ/11WT CM models, n = 4 and GNAQ/11Mut or CYSLTR2Mut UM models, n = 5. f, Representative images of hematoxylin and eosin (H&E) and Melan A immunohistochemistry of UM patients’ tumor samples, n = 7 biopsies. Percentage of tumor content, oncogenic mutation and BAP1 mutational status are shown. Scale bar, 50 μm. g, Box plots of IP4 levels shown as µg g−1 of tumor tissue of GNAQ/11WT CM patients’ samples, n = 8 and GNAQ/11Mut UM patients’ samples, n = 7. All biopsies are represented by two distinct histological sections (indicated as matching-color dots), except two biopsies per tumor type each is represented by one section. h, Schematic model describing the mechanism of INPP5A dependency in GNAQ/11Mut UM cells. Gαq/11, GNAQ/11 proteins; Ca++, calcium. All data are presented as mean ± s.e.m.; P values were determined by two-tailed, unpaired Student’s t-test (a–c,e,g). Two-tailed Pearson’s correlation with 95% confidence interval (d). Box plots show the 25th to 75th percentiles, the center line depicts the median and whiskers depict minimum and maximum values (a–c,e,g).
