Description
Objectives: Heterogeneous hypoxic areas are hallmark of most breast tumors. Exposure to hypoxia drives selection for cancer cell populations with more aggressive and resistant phenotypes. The aim was to characterize alterations in the proteome in MDA-MB-231 (mda231) and MDA-MB-436 (mda436) during long-term adaptation to mild hypoxia.Materials and Methods: Cell cultures were exposed to hypoxia (2%O2) for 4 subcultures; normoxic cultures (19.6 %O2) were controls. Peptides obtained by filter-aided sample preparation and tryptic digestion were analyzed by NanoUPLC MSE (Waters). Identification and label-free quantification of proteins was performed using PLGS and Progenesis QI (Waters). Statistical enrichment analyses were performed using open-source tools g:Profiler, GSEA and Panther.
Results:
~2420 proteins were reliably identified. Statistically significant at least 2 fold differences in normalized abundances of 417 (94↑, 323↓) and 175 (119↑, 56↓) proteins in mda231 and mda436, respectively, were observed in hypoxia vs normoxia. Hypoxia had statistically significant effect on carbon metabolism, biosynthesis of amino acids and aminoacyl-tRNAs, metabolism of proteins, ribosome assembly in mda231, and endomembrane system organization and cellular adhesion molecules in mda436.
Conclusions:
Adaptation to hypoxia in cancer cells involves re-organization of carbon and amino acid metabolism and protein synthesis. Main identified alterations were related to protein metabolism.
| Period | 17 Jun 2019 → 19 Jun 2019 |
|---|---|
| Event title | FEBS3+ conference |
| Event type | Conference |
| Location | Riga, LatviaShow on map |
| Degree of Recognition | International |