Peer Reviewed

1

Document Type

Article

Publication Date

1-7-2016

Keywords

Colorectal cancer, ER Stress, Calnexin, GRP78, GRP94, UPR (unfolded protein response)

Funder/Sponsor

Health Research Board. Science Foundation Ireland. European Union

Comments

The original article is available at www.biomedcentral.com

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.

Disciplines

Physics | Physiology

Citation

Ryan D, Carberry S, Murphy ÁC, Lindner AU, Fay J, Hector S, McCawley N, Bacon O, Concannon CG, Kay EW, McNamara DA, Prehn JH. Calnexin, an ER-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer. Journal Translational Medicine. 2016;14(1):196.

PubMed ID

27369741

DOI Link

10.1186/s12967-016-0948-z

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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