BACKGROUND: Cancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of @entity5 . Dysregulated autophagy is highly prevalent in many types of @entity5 including @entity788 and has been implicated in cytoprotection and @entity5 promotion. This study aimed to investigate the role of autophagy in regulating @entity5 stemness and chemoresistance of @entity788 . METHODS: The correlation between autophagy and CSCs and its clinical significance were analyzed using @entity788 tissue microarrays. Genetic and pharmacological approaches were applied to explore the function of autophagy on CSC activity and @entity136 resistance of @entity788 cells in vitro and in vivo. RESULTS: @entity21684 expression positively correlated with the expression of CSC markers @entity4975 dehydrogenase 1 ( @entity14215 ), @entity1759 , and @entity5439 in @entity788 tissues. High coexpression of @entity21684 / @entity14215 was associated with both poor overall survival and progression-free survival. In @entity788 cell lines, higher @entity21684 -II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing @entity10614 , @entity10615 , and @entity8783 or the administration of autophagy inhibitor @entity503 markedly reduced the CSC populations, @entity14215 activity, sphere formation, and resistance to @entity136 in vitro and in vivo. Furthermore, @entity1096 ( @entity1096 ) was found to stimulate @entity21684 -II, @entity14215 , @entity1759 , and @entity5439 expression in PANC-1 cells, whereas this effect could be prevented by @entity1096 knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of @entity1096 , only the inhibitor of NF-kB activation, BAY 1170-82, could effectively counteract @entity1096 -induced autophagy and CSC activity. According to the histochemical results, @entity788 @entity1 manifesting high levels of @entity1096 / @entity21684 / @entity14215 and @entity1096 / @entity1759 / @entity5439 had poor survival. CONCLUSIONS: Induction of autophagy mediated by @entity1096 /NF-kB signaling is required for maintenance of pancreatic CSC activity. Combination of @entity136 with pharmacological autophagy inhibitors is a promising therapeutic strategy for @entity788 .

Blockade of autophagy reduces @entity788 stem cell activity and potentiates the tumoricidal effect of XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity788 :: ('MESH:D010190', 'Disease') :: ['pancreatic cancer'] @entity4975 :: ('D000079', 'Chemical') :: ['aldehyde'] @entity503 :: ('MESH:D002738', 'Chemical') :: ['chloroquine'] @entity5439 :: ('8842', 'Gene') :: ['CD133'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity10614 :: ('9474', 'Gene') :: ['ATG5'] @entity1759 :: ('960', 'Gene') :: ['CD44'] @entity8783 :: ('8678', 'Gene') :: ['BECN1'] @entity10615 :: ('10533', 'Gene') :: ['ATG7'] @entity1096 :: ('6696', 'Gene') :: ['OPN', 'osteopontin'] @entity14215 :: ('216', 'Gene') :: ['ALDH1'] @entity21684 :: ('84557', 'Gene') :: ['LC3'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine']
@entity136 :: (MESH:C056507,Chemical) :: ['gemcitabine']
