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>