Function from within: Autophagy induction by HPSE/heparanase--new possibilities for intervention.

HPSE (heparanase) is the predominant enzyme in mammals capable of cleaving heparan sulfate, an activity highly implicated in cellular invasion and tumor metastasis. HPSE expression is induced in many types of cancer and increased HPSE levels are most often associated with increased tumor metastasis and reduced patient survival post operation. In addition, HPSE induction is associated with progression of the primary tumors but the mechanism(s) underlying tumor expansion by HPSE have not been sufficiently resolved. Our results establish a role for heparanase in modulating autophagy in normal and malignant cells, thereby conferring growth advantages as well as resistance to chemotherapy.