Additional file 1 of Human pancreatic cancer patients with Epithelial-to-Mesenchymal Transition and an aggressive phenotype show a disturbed balance in Protein Phosphatase Type 2A expression and functionality
Creators: name: van Pelt, Jos
name: Meeusen, Bob
name: Derua, Rita
name: Guffens, Liesbeth
name: Van Cutsem, Eric
name: Janssens, Veerle
name: Verslype, Chris
Publisher: name: figshare
Year: 2024
Subjects: subject: Biochemistry
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer

description: Additional file 1: Figure S1A. Non-comprehensive overview of major growth signaling functions of PP2A complexes. A key mechanism by which PP2A exerts its tumor suppressive role resides in controlling several components downstream of RAS signaling, including PI3K/AKT, MEK/ERK and JAK/STAT, thereby preventing anomalous cell survival, growth and migration. PP2A is also more directly involved in preventing activation of diverse proto-oncogenes, including β-catenin and c-MYC, as well as in promoting activation of major tumor suppressors, such as p53 and pRb. Other established roles of PP2A occur in regulation of apoptosis, autophagy, cell division and protein synthesis. Figure S1B. Structural diversity of PP2A complexes, and their regulation by cellular inhibitors and activators. Functional PP2A complexes consist of one C and one A subunit (each encoded by two different human genes), or one C, one A and one B-type subunit (encoded by 15 different human genes, some of which give rise to multiple isoforms). Additional regulation of phosphatase activity or holoenzyme assembly occurs by endogenous cellular PP2A inhibitory proteins, such as SET, ANP32A, TIPRL, CIP2A, PME-1/PPME-1 and ARPP19, and cellular PP2A activators, such as IGBP1 and PTPA/PPP2R4. Table S1. Genes and search terms that were used to investigate the expression datasets: PP2A-search terms, PDAssign and IPA-EMT. Table S2. Spearman correlation and differentially gene expression for GSE15471, GSE16515, GSE101448 and calculated means. Legend: Table S2A. For dataset GSE15471, GSE16515 and GSE101448, the Spearman correlation (SP) and corresponding p was computed for the PP2A-genes. The mean Spearman correlation (SPmean: tumor = 1 vs non-tumor = 0) and the median for p-value was computed and expressed as 10log. Table S2B. Differential gene expression (DELTA) was also computed (tumor vs non-tumor as 2log values) and the mean was calculated (meanDELTA). A t-test was computed for the individual gens in each dataset followed by calculation of median p-value (10log). Table S2C. Spearman correlation for EMT-genes. Table S2D. Differential gene expression for EMT genes. The in this paper used GSE datasets are publicly accessible through the NCBI website ( https://www.ncbi.nlm.nih.gov/ ). Table S3. RNA expression in clone OA7G vs control Panc-1 cells. The 2log fold change for PP2A and EMT genes was calculated for resistant clone OA7G vs untreated Panc-1 cells (FDR = false discovery rate, ns = not significant, nd = not determined). Table S4. Differential protein expression in Panc-1 cells exposed to Okadaic acid and clones. Protein composition of Panc-1 cells (Contr), cells exposed to OA for 24 h (OA-24) and the resistant clones OA7A and OA7G was determined. The 2log fold change (with corresponding FDR) for PP2A (A) and EMT genes (B) was calculated relative to untreated Panc-1 cells in the first block of 6 columns. In the second block, differences between the clones or between the clones and OA-24 were calculated. An FDR smaller than 0.05 is indicated in green, when FDR is between 0.05 and 0.20 this is indicated in yellow. (FDR = false discovery rate, ns = not significant, FDR &gt; 0.20). Supplementary Material and Methods: RNA sequencing procedure.