title: Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.|Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Deborah
authors.initials: D
authors.lastname: Ryan
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: Steven
authors.initials: S
authors.lastname: Carberry
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: Áine C
authors.initials: ÁC
authors.lastname: Murphy
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: Andreas U
authors.initials: AU
authors.lastname: Lindner
authors.affiliation: Department of Pathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin 9, Ireland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Fay
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hector
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.|Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: McCawley
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.|Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Orna
authors.initials: O
authors.lastname: Bacon
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.|Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Caoimhin G
authors.initials: CG
authors.lastname: Concannon
authors.affiliation: Department of Pathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin 9, Ireland.
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.affiliation: Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: McNamara
authors.affiliation: Department of Physiology and Medical Physics, Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland. prehn@rcsi.ie.
authors.forename: Jochen H M
authors.initials: JH
authors.lastname: Prehn
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D037281:Calnexin / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D012004:Rectal Neoplasms / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D037281:Calnexin; D005472:Fluorouracil
keywords: Calnexin; Colorectal cancer; ER Stress; GRP78; GRP94; UPR (unfolded protein response)