Analysis of Unfolded Protein Response Activation in Colon Adenocarcinoma Epithelial Cells: A Proteomic Study.

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Vivier, Solange | Bray, Fabrice | Flament, Stephanie | Guilbert, Lucile | Renaud, F. | Rolando, Christian | Launay, David | Dubucquoi, Sylvain | Sobanski, Vincent

Edité par CCSD -

International audience. Purpose: High throughput technologies have identified molecular patterns in colorectal cancer (CRC) cells, aiding in modelingresponses to anti-cancer treatments. The different responses observed depend on the type of cancer, the tumour grade and thefunctional programme of the cancer cells. Recent studies suggest that the unfolded protein response (UPR), autophagy andapoptosis could be involved in treatment resistance mechanisms by interacting with the tumour microenvironment (TME).Experimental Design: We analysed by LC-MS/MS the proteome of two representative colon adenocarcinoma epithelial cell linesfrom different tumour grades (CCL-233 and CCL-221) at the basal state or after the UPR induction.Results: Cell lines expressed a different proteome on about 10% of their total proteins identified, especially on UPR, autophagyand apoptosis pathways proteins at basal state. After UPR induction, the proteome of the cells was modified with a greater adaptiveresponse to cellular stress in CCL-221 cells where the UPR was strongly activated at the basal state.Conclusions and Clinical Relevance: CRC cell lines at different tumour grades expressed different functional programmes atthe proteomic level and were characterised by different responses to the UPR induction. This study suggests that baseline cancercell stress status could have an impact on the efficiency of cancer therapies.

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