<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Siddiqui, Shoib S</style></author><author><style face="normal" font="default" size="100%">Vaill, Michael</style></author><author><style face="normal" font="default" size="100%">Do, Raymond</style></author><author><style face="normal" font="default" size="100%">Khan, Naazneen</style></author><author><style face="normal" font="default" size="100%">Verhagen, Andrea L</style></author><author><style face="normal" font="default" size="100%">Zhang, Wu</style></author><author><style face="normal" font="default" size="100%">Lenz, Heinz-Josef</style></author><author><style face="normal" font="default" size="100%">Johnson-Pais, Teresa L</style></author><author><style face="normal" font="default" size="100%">Leach, Robin J</style></author><author><style face="normal" font="default" size="100%">Fraser, Gary</style></author><author><style face="normal" font="default" size="100%">Wang, Charles</style></author><author><style face="normal" font="default" size="100%">Feng, Gen-Sheng</style></author><author><style face="normal" font="default" size="100%">Nissi M Varki</style></author><author><style face="normal" font="default" size="100%">Ajit Varki</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Human‐specific polymorphic pseudogenization of SIGLEC12 protects against advanced cancer progression.</style></title><secondary-title><style face="normal" font="default" size="100%">FASEB Bioadv</style></secondary-title><alt-title><style face="normal" font="default" size="100%">FASEB Bioadv</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021 Feb</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">3</style></volume><pages><style face="normal" font="default" size="100%">69-82</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Compared with our closest living evolutionary cousins, humans appear unusually prone to develop carcinomas (cancers arising from epithelia). The gene, which encodes the Siglec-XII protein expressed on epithelial cells, has several uniquely human features: a fixed homozygous missense mutation inactivating its natural ligand recognition property; a polymorphic frameshift mutation eliminating full-length protein expression in ~60%-70% of worldwide human populations; and, genomic features suggesting a negative selective sweep favoring the pseudogene state. Despite the loss of canonical sialic acid binding, Siglec-XII still recruits Shp2 and accelerates tumor growth in a mouse model. We hypothesized that dysfunctional Siglec-XII facilitates human carcinoma progression, correlating with known tumorigenic signatures of Shp2-dependent cancers. Immunohistochemistry was used to detect Siglec-XII expression on tissue microarrays. PC-3 prostate cancer cells were transfected with Siglec-XII and transcription of genes enriched with Siglec-XII was determined. Genomic status was determined for four different cancer cohorts. Finally, a dot blot analysis of human urinary epithelial cells was established to determine the Siglec-XII expressors versus non-expressors. Forced expression in a null carcinoma cell line enriched transcription of genes associated with cancer progression. While Siglec-XII was detected as expected in ~30%-40% of normal epithelia, ~80% of advanced carcinomas showed strong expression. Notably, &amp;gt;80% of late-stage colorectal cancers had a functional allele, correlating with overall increased mortality. Thus, advanced carcinomas are much more likely to occur in individuals whose genomes have an intact gene, likely because the encoded Siglec-XII protein recruits Shp2-related oncogenic pathways. The finding has prognostic, diagnostic, and therapeutic implications.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">2</style></issue><custom1><style face="normal" font="default" size="100%">&lt;p&gt;https://www.ncbi.nlm.nih.gov/pubmed/33615152?dopt=Abstract&lt;/p&gt;
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