Aberrant expression of Sec61α in esophageal cancers
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The heterotrimeric Sec61α translocon complex is topological located in the membrane of the endoplasmic reticulum (ER) and allows protein transport and calcium across the membrane. Recently, aberrant expression of Sec proteins was linked to carcinogenesis and prognosis of patients.
Materials and methods
Here, we analysed the role of Sec61α in esophageal cancer, and we analysed Sec61α staining on a tissue microarray containing more than 600 esophageal cancer specimens by immunohistochemistry.
Sec61α staining was always strong in benign esophagus, but was only found in 5% of interpretable esophageal adenocarcinomas (EACs) and 14.5% of squamous cell carcinomas (ESCCs). Reduced Sec61α staining was not strongly linked to tumor phenotype in both subgroups of esophageal cancers and was unrelated to clinical outcome of patients (EACs: p = 0.8051 and ESCCs: p = 0.2751).
Thus, Sec61α measurement has not an additional prognostic benefit for the patients.
KeywordsSec61α Esophageal cancer Tissue microarray
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
The utilization of tissues and clinical data was according to the Hamburger Krankenhaus Gesetz (§12 HmbKHG) and approved by our local Ethical Committee.
- Becker T, Bhushan S, Jarasch A, Armache J-P, Funes S, Jossinet F, Gumbart J, Mielke T, Berninghausen O, Schulten K, Westhof E, Gilmore R, Mandon EC, Beckmann R (2009) Structure of monomeric yeast and mammalian Sec61 complexes interacting with the translating ribosome. Science 326:1369–1373. https://doi.org/10.1126/science.1178535 CrossRefGoogle Scholar
- Casper M, Weber SN, Kloor M, Müllenbach R, Grobholz R, Lammert F, Zimmer V (2013) Hepatocellular carcinoma as extracolonic manifestation of Lynch syndrome indicates SEC63 as potential target gene in hepatocarcinogenesis. Scand J Gastroenterol 48:344–351. https://doi.org/10.3109/00365521.2012.752030 CrossRefGoogle Scholar
- Giunti R, Gamberucci A, Fulceri R, Bánhegyi G, Benedetti A (2007) Both translocon and a cation channel are involved in the passive Ca2+ leak from the endoplasmic reticulum: a mechanistic study on rat liver microsomes. Arch Biochem Biophys 462:115–121. https://doi.org/10.1016/j.abb.2007.03.039 CrossRefGoogle Scholar
- Lomax RB, Camello C, van Coppenolle F, Petersen OH, Tepikin AV (2002) Basal and physiological Ca(2+) leak from the endoplasmic reticulum of pancreatic acinar cells. Second messenger-activated channels and translocons. J Biol Chem 277:26479–26485. https://doi.org/10.1074/jbc.M201845200 CrossRefGoogle Scholar
- Lu Z, Zhou L, Killela P, Rasheed AB, Di C, Poe WE, McLendon RE, Bigner DD, Nicchitta C, Yan H (2009) Glioblastoma proto-oncogene SEC61gamma is required for tumor cell survival and response to endoplasmic reticulum stress. Cancer Res 69:9105–9111. https://doi.org/10.1158/0008-5472.CAN-09-2775 CrossRefGoogle Scholar
- Mori Y, Sato F, Selaru FM, Olaru A, Perry K, Kimos MC, Tamura G, Matsubara N, Wang S, Xu Y, Yin J, Zou T-T, Leggett B, Young J, Nukiwa T, Stine OC, Abraham JM, Shibata D, Meltzer SJ (2002) Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers. Cancer Res 62:3641–3645Google Scholar
- Park E, Rapoport TA (2012) Mechanisms of Sec61/SecY-mediated protein translocation across membranes. Annu Rev Biophys 41:21–40. https://doi.org/10.1146/annurev-biophys-050511-102312 CrossRefGoogle Scholar
- Schulmann K, Brasch FE, Kunstmann E, Engel C, Pagenstecher C, Vogelsang H, Krüger S, Vogel T, Knaebel H-P, Rüschoff J, Hahn SA, Knebel-Doeberitz MV, Moeslein G, Meltzer SJ, Schackert HK, Tympner C, Mangold E, Schmiegel W (2005) HNPCC-associated small bowel cancer: clinical and molecular characteristics. Gastroenterology 128:590–599CrossRefGoogle Scholar
- Shao S, Hegde RS (2011) Membrane protein insertion at the endoplasmic reticulum. Annu Rev Cell Dev Biol 27:25–56. https://doi.org/10.1146/annurev-cellbio-092910-154125 CrossRefGoogle Scholar
- Song Y, Li L, Ou Y, Gao Z, Li E, Li X, Zhang W, Wang J, Xu L, Zhou Y, Ma X, Liu L, Zhao Z, Huang X, Fan J, Dong L, Chen G, Ma L, Yang J, Chen L, He M, Li M, Zhuang X, Huang K, Qiu K, Yin G, Guo G, Feng Q, Chen P, Wu Z, Wu J, Ma L, Zhao J, Luo L, Fu M, Xu B, Chen B, Li Y, Tong T, Wang M, Liu Z, Lin D, Zhang X, Yang H, Wang J, Zhan Q (2014) Identification of genomic alterations in oesophageal squamous cell cancer. Nature 509:91–95. https://doi.org/10.1038/nature13176 CrossRefGoogle Scholar
- Watanabe G, Kaganoi J, Imamura M, Shimada Y, Itami A, Uchida S, Sato F, Kitagawa M (2001) Progression of esophageal carcinoma by loss of EGF-STAT1 pathway. Cancer J 7:132–139Google Scholar