Figure 2.
STAG2, PAXIP1, and PAGR1 effects are highly correlated in human cancer cell lines and PAXIP1/PAGR1 are tumor suppressive in KRAS-driven lung tumors in vivo. (a) Genes with the most correlated effects with STAG2 inactivation from the DepMap. Cell lines with STAG2 mutations were excluded. PAXIP1 and PAGR1 are colored bars. Core cohesin complex genes are white bars. (b and c) Gene effects for PAXIP1 and STAG2 inactivation (b) and for PAGR1 and STAG2 inactivation (c). Each dot represents a cell line with an oncogenic mutation at codons 12 or 13 of KRAS. Cell lines with STAG2 mutations were excluded. Lung adenocarcinoma (LUAD) cell lines are shown as black dots. Spearman’s r and Pearson rho for all cell lines and for LUAD cell lines are indicated. (d) Tumor initiation with a pool of barcoded Lenti-U6BCsgRNA/Cre Tuba-seqUltra vectors. Genotype and number of mice are indicated. Tuba-seqUltra was performed on each tumor-bearing lung 15 wk after tumor initiation, followed by analyses to quantify tumorigenesis. (e) Relative mean tumor size (normalized to sgInert). Mean ± 95% confidence intervals are shown. Dotted line indicates no effect. (f) Tumor sizes at the indicated percentiles for tumors with sgRNA targeting Stag2, Paxip1, or Pagr1 (normalized to sgInert) in KT;H11LSL-Cas9 mice. Each gene was targeted with three sgRNAs. Error bars indicate 95% confidence intervals. Dotted line indicates no effect. Data represents one replicate of two independent experiments. (g) Tumor initiation with the indicated Lenti-sgRNA/Cre vectors in separate cohorts of KT and KT;H11LSL-Cas9 mice. Number of mice in each group is indicated. Tumor burden was quantified 15 wk after tumor initiation. (h) Representative brightfield and fluorescence images of lung lobes and histology from the indicated groups of mice. Top scale bars and middle scale bars, 5 mm. Lower scale bars, 500 μm. (i) Lung weights of mice in each group. Each dot represents a mouse and the bar is the mean. ****P value <0.0001 by unpaired t test. Data represent one replicate of two independent experiments. Raw values and significance of each effect are shown in Table S2.

STAG2, PAXIP1, and PAGR1 effects are highly correlated in human cancer cell lines and PAXIP1/PAGR1 are tumor suppressive in KRAS-driven lung tumors in vivo. (a) Genes with the most correlated effects with STAG2 inactivation from the DepMap. Cell lines with STAG2 mutations were excluded. PAXIP1 and PAGR1 are colored bars. Core cohesin complex genes are white bars. (b and c) Gene effects for PAXIP1 and STAG2 inactivation (b) and for PAGR1 and STAG2 inactivation (c). Each dot represents a cell line with an oncogenic mutation at codons 12 or 13 of KRAS. Cell lines with STAG2 mutations were excluded. Lung adenocarcinoma (LUAD) cell lines are shown as black dots. Spearman’s r and Pearson rho for all cell lines and for LUAD cell lines are indicated. (d) Tumor initiation with a pool of barcoded Lenti-U6BCsgRNA/Cre Tuba-seqUltra vectors. Genotype and number of mice are indicated. Tuba-seqUltra was performed on each tumor-bearing lung 15 wk after tumor initiation, followed by analyses to quantify tumorigenesis. (e) Relative mean tumor size (normalized to sgInert). Mean ± 95% confidence intervals are shown. Dotted line indicates no effect. (f) Tumor sizes at the indicated percentiles for tumors with sgRNA targeting Stag2, Paxip1, or Pagr1 (normalized to sgInert) in KT;H11LSL-Cas9 mice. Each gene was targeted with three sgRNAs. Error bars indicate 95% confidence intervals. Dotted line indicates no effect. Data represents one replicate of two independent experiments. (g) Tumor initiation with the indicated Lenti-sgRNA/Cre vectors in separate cohorts of KT and KT;H11LSL-Cas9 mice. Number of mice in each group is indicated. Tumor burden was quantified 15 wk after tumor initiation. (h) Representative brightfield and fluorescence images of lung lobes and histology from the indicated groups of mice. Top scale bars and middle scale bars, 5 mm. Lower scale bars, 500 μm. (i) Lung weights of mice in each group. Each dot represents a mouse and the bar is the mean. ****P value <0.0001 by unpaired t test. Data represent one replicate of two independent experiments. Raw values and significance of each effect are shown in Table S2.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal