Triplex profiling of functionally distinct chaperones (ERp29/PDI/BiP) reveals marked heterogeneity of the endoplasmic reticulum proteome in cancer.
The biomedical need for streamlined approaches to monitor proteome dynamics is growing rapidly. This study examined the ability of a knowledge-based triplex-profiling strategy (i.e., three functionally distinct chaperones, ERp29/PDI/BiP) to clarify uncertainties about how cancer affects the endoplasmic reticulum (ER) proteome. Investigating a wide range of samples at the tissue and cellular levels (>114 samples from 9 tissues of origin), we obtained consistent evidence that the ER proteome undergoes a major but variable expansion in cancer. Three factors having a strong influence on the ER proteome were identified (cancer-cell type, growth rate, culture mode), and the functionally enigmatic chaperone ERp29 was linked distinctively to histogenetic aspects of tumorigenesis. These findings justify pursuit of the ER-proteome as a medical target in cancer, validate ERp29/PDI/BiP profiling as a streamlined yet powerful measure of ER-proteome dynamics, and suggest that biomarker sets based on distinct functionalities could have broader biomedical utility.
Shnyder
Steven D
SD
Department of Biochemistry, University of Otago, New Zealand.
Mangum
Jonathan E
JE
Hubbard
Michael J
MJ
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007774:Lactation / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology; D040081:Protein Array Analysis; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous
D014408:Biomarkers, Tumor; C491738:ERP29 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C110909:Erp29 protein, rat; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020543:Proteome; D019704:Protein Disulfide-Isomerases