Cisplatin-induced proteome changes in ovatian cancer cells

ABSTRACT: Tumors easily acquire resistance to individual drugs and drug combinations thereby limiting the treatment effectiveness. Drug-stressed tumor cells secrete components that promote the survival of recipient cells and repopulation of damaged tumors. We have previously found that therapy-induced secretomes are enriched with spliceosomal proteins. The behavior of splicing-associated genes in response to chemotherapeutic drugs is poorly understood. We show that a severely stressed cell dramatically down-regulates spliceosomal proteins by secreting them into the extracellular space, reducing the expression of the respective genes, and disrupting the splicing. Our meta-analysis indicates that drugs with different action mechanisms cause a correlated decrease in the transcription of genes involved in spliceosome and mitotic cell cycle pathways and induce similar intron retention patterns in these genes. The key transcription factors regulating the concerted change in transcription are MYC, E2F1, TP53, and WT1. Based on the correlation analysis with siRNA data, we conclude that a decrease in the representation of intracellular spliceosomal proteins in response to stress is aimed at the cell cycle arrest. At the expression and processing levels, we demonstrate that a strong interplay between splicing-associated and cell cycle genes develops in stressed cancer cells.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Ovarian Surface Epithelial Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Georgij Arapidi  

LAB HEAD: Georgij Pavlovich Arapidi

PROVIDER: PXD007615 | Pride | 2018-05-22

REPOSITORIES: Pride