Fig. 5: IP3R3 expression is reduced in SMARCA4/2-deficient cancers. | Nature Communications

Fig. 5: IP3R3 expression is reduced in SMARCA4/2-deficient cancers.

From: SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria

Fig. 5

a Correlation of ITPR3 and SMARCA2 (A2) mRNA in ovarian (n = 11) and lung (n = 48) cancer cell lines with low expression of SMARCA4 (A4). Expression data were obtained from Cancer Cell Line Encyclopedia (CCLE) in reads per kilobase million (RPKM)42. A4Low, bottom quartile. r: Pearson correlation; p: p value (two-tailed). b Immunoblots of lung cancer cell lines with indicated SMARCA4/2 (A4/2) status. Pro proficient, def deficient; * KRAS mutant. c Correlation of ITPR3 and SMARCA2 mRNA in ovarian cancer (n = 89) and lung adenocarcinoma (LUAD, n = 128) patient tumors with low expression of SMARCA4. Gene expression data were obtained from UCSC Xena in fragments per kilobase million (FPKM). A4Low, bottom quartile. r, Pearson correlation; p, p value (two-tailed). d ITPR3 mRNA expression in SCCOHT and ovarian cancer patient tumors. TCGA ovarian cancers (OV) (n = 379) were stratified based on SMARCA4/2 expression as indicated in Supplementary Fig. 2b. ITPR3 expression in FPKM was normalized to ACTB. H: high; L: low. One-way ANOVA Brown–Forsythe and Welch tests followed by Dunnett’s test for multiple comparisons to A4HA2H, p values (p): A4HA2L—0.3830, A4LA2H—0.0009, A4LA2L < 0.0001, SCCOHT—0.0108, or two-tailed t-test between A4LA2L group and SCCOHT, p = 0.4953. Representative images (e, g) and H-score (f, h) of immunohistochemistry analysis for IP3R3 and SMARCA4 expression in patient tumors. e, f HGSC (n = 49) and SCCOHT (n = 45). g, h NSCLC (n = 59). Scale bar, 100 μm. Mann–Whitney test (two-tailed), p values (p): f 0.0066, h 0.0270. i Tumor growth in H1703 xenograft models ± exogenous SMARCA4 expression. Doxycycline (Dox) was given daily starting on day 21 to induce SMARCA4. Upper, tumor size; lower, endpoint tumor weight. Mean ± SEM, − Dox (n = 4 animals), + Dox (n = 6 animals), two-way ANOVA (upper), two-tailed t-test (lower), p values (p): upper—0.0014, lower—0.0008. Representative images (j) and digital quantification (k) of immunohistochemistry analysis in endpoint tumors described in i. Scale bar, 100 μm. Mean ± SD, − Dox (n = 4), + Dox (n = 6), two-tailed t-test (lower), p values (p): upper, middle <0.0001; lower—0.0041. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns not significant.

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