10779/rcsi.10793456.v1 Deborah Ryan Deborah Ryan Steven Carberry Steven Carberry Áine C. Murphy Áine C. Murphy Andreas U. Lindner Andreas U. Lindner Joanna Fay Joanna Fay Suzanne Hector Suzanne Hector Niamh McCawley Niamh McCawley Orna Bacon Orna Bacon Caoimhín G. Concannon Caoimhín G. Concannon Elaine W. Kay Elaine W. Kay Deborah A. McNamara Deborah A. McNamara Jochen HM Prehn Jochen HM Prehn Calnexin, an ER-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer. Royal College of Surgeons in Ireland 2019 Colorectal cancer ER Stress Calnexin GRP78 GRP94 UPR (unfolded protein response) Physiology Medical Physics 2019-11-22 17:05:53 Journal contribution https://repository.rcsi.com/articles/journal_contribution/Calnexin_an_ER-induced_protein_is_a_prognostic_marker_and_potential_therapeutic_target_in_colorectal_cancer_/10793456 <p><strong>BACKGROUND:</strong> Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance.</p> <p><strong>METHODS:</strong> The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells.</p> <p><strong>RESULTS:</strong> There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy.</p> <p><strong>CONCLUSION:</strong> Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.</p>