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

• Published in: Proteomics. Clinical applications 2024-11, Vol.18 (6), p.e202400008-n/a
• Main Authors: Vivier, Solange, Bray, Fabrice, Flament, Stéphanie, Guilbert, Lucile, Renaud, Florence, Rolando, Christian, Launay, David, Dubucquoi, Sylvain, Sobanski, Vincent
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Apoptosis; Autophagy; Cancer; Cancer therapies; Cell activation; Cell Line, Tumor; Cellular stress response; Colon; Colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; colorectal cancer; Colorectal carcinoma; Design of experiments; endoplasmic reticulum stress; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelium; Humans; LC‐MS/MS; Life Sciences; Protein folding; Proteins; Proteome - metabolism; Proteomes; Proteomics; Treatment resistance; Tumor cell lines; Tumor microenvironment; Tumors; Unfolded Protein Response
• ISSN: 1862-8346; 1862-8354; 1862-8354
• DOI: 10.1002/prca.202400008

ABSTRACT Purpose High throughput technologies have identified molecular patterns in colorectal cancer (CRC) cells, aiding in modeling responses to anti‐cancer treatments. The different responses observed depend on the type of cancer, the tumour grade and the functional programme of the cancer cells. Recent studies suggest that the unfolded protein response (UPR), autophagy and apoptosis 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 lines from 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, autophagy and apoptosis pathways proteins at basal state. After UPR induction, the proteome of the cells was modified with a greater adaptive response 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 at the proteomic level and were characterised by different responses to the UPR induction. This study suggests that baseline cancer cell stress status could have an impact on the efficiency of cancer therapies.