Skip to main content
. 2021 Jun 18;81(16):4319–4331. doi: 10.1158/0008-5472.CAN-20-3651

Figure 5.

Figure 5. CIP2A is essential for survival of TP53/BRCA-mutant BLBC cells and drives proliferative signaling. A, Expression of CIP2A mRNA in indicated molecular breast cancer subtypes. Data derived from TCGA. P values by the unpaired t test. B, Disease-free survival of CIP2A high (n = 15) and CIP2A low (n = 45) expressing basal-like patients with TNBC in GSE21653 cohort. C, Disease-free survival of CIP2A high (n = 45) and CIP2A low (n = 132) expressing non-basal-like (HER2+, luminal A, luminal B, and normal-like) patients with breast cancer in GSE21653 cohort. D, Overall survival of CIP2A high (n = 12) and CIP2A low (n = 51) basal-like patients with TNBC in FinHer cohort. E, Overall survival of CIP2A high (n = 17) and CIP2A low (n = 47) non-basal like TNBC patients based IHC analysis from FinHer cohort. B–E, P values calculated by the log-rank test. F, CIP2A dependence of breast cancer cell lines with CERES score < −0.4 from DepMap portal (Avana 2020Q1). Lower CERES scores indicate that the cell line is more dependent on CIP2A. Color coding indicates the breast cancer subtype of the cell line based on PAM50 classification. G, Colony growth assays conducted on mammary tumor cell lines isolated from basal-type (KB1P#1 and KB1P#2: Brca1 and Trp53 mutant) and invasive lobular carcinoma (ILC)-type (KEP#1 and KEP#2: E-cadherin and Trp53 mutant) mouse models; Cip2a was knocked out using CRISPR/Cas9 using two unique gRNAs. Western blots from the same samples probed for CIP2A below. Shown are representative images of at least two independent biological repeats for each cell line. H, Summary of CIP2A dependence on colony growth of indicated TP53-mutant TNBC cell lines transfected with Mock, nontargeting siRNA (siSCR), or three unique CIP2A-targeting siRNAs (siCIP2A #1, #2, #3). Colony areas were quantified and normalized to siSCR. I, Gene set enrichment analysis (GSEA) conducted on differentially expressed genes obtained from RNA-seq of HCC38 cells depleted with three unique CIP2A siRNAs. J, HCC38 cells transfected with SCR or CIP2A siRNAs for 72 hours and immunoblotted for indicated protein.

CIP2A is essential for survival of TP53/BRCA-mutant BLBC cells and drives proliferative signaling. A, Expression of CIP2A mRNA in indicated molecular breast cancer subtypes. Data derived from TCGA. P values by the unpaired t test. B, Disease-free survival of CIP2A high (n = 15) and CIP2A low (n = 45) expressing basal-like patients with TNBC in GSE21653 cohort. C, Disease-free survival of CIP2A high (n = 45) and CIP2A low (n = 132) expressing non-basal-like (HER2+, luminal A, luminal B, and normal-like) patients with breast cancer in GSE21653 cohort. D, Overall survival of CIP2A high (n = 12) and CIP2A low (n = 51) basal-like patients with TNBC in FinHer cohort. E, Overall survival of CIP2A high (n = 17) and CIP2A low (n = 47) non-basal like TNBC patients based IHC analysis from FinHer cohort. B–E,P values calculated by the log-rank test. F,CIP2A dependence of breast cancer cell lines with CERES score < −0.4 from DepMap portal (Avana 2020Q1). Lower CERES scores indicate that the cell line is more dependent on CIP2A. Color coding indicates the breast cancer subtype of the cell line based on PAM50 classification. G, Colony growth assays conducted on mammary tumor cell lines isolated from basal-type (KB1P#1 and KB1P#2: Brca1 and Trp53 mutant) and invasive lobular carcinoma (ILC)-type (KEP#1 and KEP#2: E-cadherin and Trp53 mutant) mouse models; Cip2a was knocked out using CRISPR/Cas9 using two unique gRNAs. Western blots from the same samples probed for CIP2A below. Shown are representative images of at least two independent biological repeats for each cell line. H, Summary of CIP2A dependence on colony growth of indicated TP53-mutant TNBC cell lines transfected with Mock, nontargeting siRNA (siSCR), or three unique CIP2A-targeting siRNAs (siCIP2A #1, #2, #3). Colony areas were quantified and normalized to siSCR. I, Gene set enrichment analysis (GSEA) conducted on differentially expressed genes obtained from RNA-seq of HCC38 cells depleted with three unique CIP2A siRNAs. J, HCC38 cells transfected with SCR or CIP2A siRNAs for 72 hours and immunoblotted for indicated protein.