The immune signal protein Siglec-XII is broken in humans. It doesn’t work the way it should. And at the same time, it increases the risk of tumors.
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Sialic acid-binding immunoglobulin-type lectins (Siglecs) are membrane signal proteins, lectins from the immunoglobulin family that binds sialic acid. They can mostly be found on the surfaces of immune cells such as phagocytes, mast cells, or NK (natural killer) cells. In mammals, we discovered a total of 14 siglecs that perform a wide variety of functions mostly when it comes to the immune system.
Of the siglecs we know of is Siglec-XII that is produced by the gene SIGLEC12 in humans. As it tends to be with genes we aren’t exactly sure how it works. It seems to have a major role when it comes to regulating macrophages where it works as an inhibiting receptor – essentially a brake. Or, to be more precise, this is how it should work as the protein seems to come with a pretty big problem. As Ajit and Nissi Varki from the University of California, San Diego say – all suggests that this siglec is broken in humanity. It isn’t capable of binding sialic acid and it contributes to abnormal cellular signalization.
The big problem comes with the fact that not only is Siglic-XII broken but also dangerous. It contributes to the development of tumors and is at least partially responsible for why humanity seems to suffer from carcinomas much more often than our nearest relatives – primates. Carcinomas are tumors created from epithelium such as colorectal carcinoma – better known as colon cancer, prostate carcinoma, breast carcinoma, or stomach carcinoma. And carcinoma accounts for about 80 % of all malignant tumors.
Some of you might now be saying, we aren’t most likely seeing all the context and that Siglec-XII must come with some benefits. But it seems that it truly doesn’t. About 70 % of all humans have a mutation that makes Siglec-XII not work. Thus, only about 30 % of humans have this gene doing work yet the team led by the Varkis found the protein in about 80 % of carcinoma samples.
Then, when the researchers experimentally increased the production of the protein in the human cell line of a prostate cancer tumor the genes associated with the growth and spread of the tumors expressed much more. At the same time, the scientists found out that patients that have colorectal carcinoma and the functioning variant of Siglec-XII have a much worse prognosis.
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