The Emerging Roles of Heparan Sulfate 3-O-Sulfotransferases in Cancer
Résumé
Alteration in the expression of heparan sulfate (HS)-modifying enzymes has beenfrequently observed in cancer. Consequently, dysregulation of the HS biosyntheticmachinery results in dramatic changes in the HS structure, thereby impacting a range ofpivotal cellular processes involved in tumorigenesis and cancer progression includingproliferation, migration, apoptosis, and immune escape. HS 3-O-sulfotransferases(HS3STs) catalyse the maturation step of glucosaminyl 3-O-sulfation within HS chains.Although seven HS3ST isozymes have been described in human,3-O-sulfation is arare modification and only a few biological processes have been described to beinfluenced by 3-O-sulfated HS. An aberrant expression of HS3STs has been reportedin a variety of cancers. Thus, it was suggested that changes in the expression of theseenzymes as a result of tumorigenesis or tumor growth may critically influence cancer cellbehavior. In accordance with this assumption, a number of studies have documented theepigenetic repression of HS3ST2 and HS3ST3A in many cancers. However, the situationis not so clear, and there is accumulating evidence that HS3ST2, HS3ST3A, HS3ST3B,and HS3ST4 may also act as tumor-promoting enzymes in a number of cancer cellsdepending on their phenotypes and molecular signatures. Inthis mini-review, we focuson the recent insights regarding the abnormal expression ofHS3STs in cancer anddiscuss the functional consequences on tumor cell behavior. In term of clinical outcome,further investigations are needed to explore the potentialvalue of HS3STs and/or their3-O-sulfated products as targets for therapeutic strategies in cancer treatment.
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