Calnexin, an ER-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer

Journal of Translational Medicine

Research

Deborah A. McNamara¹  Elaine W. Kay²  Joanna Fay²  Steven Carberry³  Jochen H. M. Prehn³  Suzanne Hector³  Andreas U. Lindner³  Áine C. Murphy³  Deborah Ryan⁴  Caoimhin G. Concannon⁴  Orna Bacon⁴  Niamh McCawley⁴ 

[1] Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland;Department of Pathology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin 9, Ireland;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 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;

关键词: Colorectal cancer;    ER Stress;    Calnexin;    GRP78;    GRP94;    UPR (unfolded protein response);   

DOI  :  10.1186/s12967-016-0948-z

 received in 2015-08-24, accepted in 2016-06-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundColorectal 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.MethodsThe 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.ResultsThere 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.ConclusionIncreased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.

【 授权许可】

CC BY   
© The Author(s) 2016