Open AccessO‐acetylation and de‐O‐acetylation of sialic acids in human colorectal carcinoma
Author(s) -
Shen Yanqin,
Kohla Guido,
Lrhorfi Aicha L.,
Sipos Bence,
Kalthoff Holger,
Gerwig Gerrit J.,
Kamerling Johannis P.,
Schauer Roland,
Tiralongo Joe
Publication year - 2004
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2003.03927.x
Subject(s) - acetylation , sialic acid , colorectal cancer , cytosol , biochemistry , chemistry , enzyme , glycosyltransferase , cancer research , biology , cancer , medicine , gene
A decrease in the level of O‐acetylated sialic acids observed in colorectal carcinoma may lead to an increase in the expression of sialyl Lewis X , a tumor‐associated antigen, which is related to progression of colorectal cancer to metastasis. The underlying mechanism for this reduction is, however, not fully understood. Two enzymes are thought to be primarily responsible for the turnover of O‐acetyl ester groups on sialic acids; sialate‐ O ‐acetyltransferase (OAT) and sialate‐ O ‐acetylesterase (OAE). We have previously reported the characterization of OAT activity from normal colon mucosa, which efficiently O‐acetylates CMP‐Neu5Ac exclusively in the Golgi apparatus prior to the action of sialyltransferase [Shen, Y., Tiralongo, J., Iwersen, M., Sipos, B., Kalthoff, H. & Schauer, R. (2002) Biol. Chem. 383 , 307–317]. In this report we describe the identification of a lysosomal and a cytosolic OAE activity in human colonic mucosa that specifically hydrolyses 9‐ O ‐acetyl groups on sialic acid. Utilizing matched resection margin and cancer tissue from colorectal carcinoma patients we provide strong evidence suggesting that the level of O‐acetylated sialic acids present in normal and diseased human colon may be dependent on the relative activities of OAT to lysosomal OAE. Furthermore, we show that the level of free cytosolic Neu5,9Ac 2 in human colon is regulated by the relative activity of the cytosolic OAE.