biostudies-literatureManouchehri JMthe National Center for Advancing Translational Sciences of the NIHNCATS NIH HHSOhio State UniversityNational Cancer InstituteNCI NIH HHSNational Institutes of Health2483989https://www.ebi.ac.uk/biostudies/studies/S-EPMC11951697biostudies-literatureUnknown26(1)The highest incidence and cancer-related mortality rate among women worldwide is due to breast cancer. Triple-negative breast cancers (TNBC) are associated with more inferior outcomes than other breast cancers because of their progressive nature and the deficit in available therapies. Therefore, there is a need for new therapeutic approaches. Our lab determined that chemotherapy induces the release of extracellular adenosine triphosphate (eATP), and, hence, augments TNBC cells' response to chemotherapy. Despite this, eATP concentrations are restricted by a variety of extracellular ATPases. We propose that, as an ATPase inhibitor, heparan sulfate (HS) would augment eATP concentrations and TNBC vulnerability induced by chemotherapy. Sulfatase 2 (SULF2) removes sulfate from HS, the functionalCancer biology & therapySulfatase 2 inhibition sensitizes triple-negative breast cancer cells to paclitaxel through augmentation of extracellular ATP.PMC11951697P30 CA016058R01 CA292020KL2 TR002734Schnell PMDatta JCherian MAGanju RKStover DZhang XRubinstein MPRamaswamy BManouchehri JMCarson WEMittra AYue YMarcho LMfalseSulfatase 2 inhibition sensitizes triple-negative breast cancer cells to paclitaxel through augmentation of extracellular ATP.The highest incidence and cancer-related mortality rate among women worldwide is due to breast cancer. Triple-negative breast cancers (TNBC) are associated with more inferior outcomes than other breast cancers because of their progressive nature and the deficit in available therapies. Therefore, there is a need for new therapeutic approaches. Our lab determined that chemotherapy induces the release of extracellular adenosine triphosphate (eATP), and, hence, augments TNBC cells' response to chemotherapy. Despite this, eATP concentrations are restricted by a variety of extracellular ATPases. We propose that, as an ATPase inhibitor, heparan sulfate (HS) would augment eATP concentrations and TNBC vulnerability induced by chemotherapy. Sulfatase 2 (SULF2) removes sulfate from HS, the functional2025-01-01T00:00:00Z2025 Dec2026-06-01T22:58:56.817Z2025-07-02T03:04:36.616ZS-EPMC119516974014034710.1080/15384047.2025.2483989