BACKGROUND: Although some molecularly targeted drugs for @entity14 are used clinically and contribute to a better prognosis, the current median survival of advanced @entity14 @entity1 is not sufficient. Autophagy, a basic cell survival mechanism mediated by recycling of cellular @entity1522 , plays an important role in @entity5 . Recently, autophagy has been highlighted as a promising new molecular target. The unfolded protein response (UPR) reportedly act in complementary fashion with autophagy in intestinal homeostasis. However, the roles of UPR in @entity694 under autophagic inhibition remain to be elucidated. We aim to clarify the inhibitory effect of autophagy on @entity694 . METHODS: We crossed @entity25634 (CreERT) and @entity15254 (flox/flox) @entity19 to generate @entity15254 (flox/flox) / @entity25634 (CreERT) @entity19 . @entity15254 (flox/flox) / @entity25634 (CreERT) @entity19 were first treated with @entity2985 /dextran @entity2397 and then injected with @entity440 to inhibit autophagy in @entity25634 -positive epithelial cells. To examine the anti- @entity5 mechanisms of autophagic inhibition, we used @entity694 cell lines harboring different @entity899 gene statuses, as well as small interfering RNAs (siRNAs) targeting @entity15254 and @entity13839 ( @entity13839 ), a chaperone to aid folding of unfolded proteins. RESULTS: @entity694 in @entity15254 (flox/flox) / @entity25634 (CreERT) @entity19 showed loss of autophagic activity and decreased @entity5 size (the total @entity5 diameter was 28.1  mm in the control and 20.7  mm in @entity15254 (flox/flox) / @entity25634 (CreERT) @entity19 , p   =   0.036). We found that @entity899 and UPR/endoplasmic reticulum (ER) stress-related proteins, such as cleaved caspase 3, and CAAT/enhancer-binding protein homologous protein, are up-regulated in @entity694 of @entity15254 (flox/flox) / @entity25634 (CreERT) @entity19 . Although @entity15254 and @entity13839 silencing, respectively, increased apoptosis in @entity899 wild type cells, @entity15254 silencing alone did not show the same effect on apoptosis in @entity899 mutant cells. However, co-transfection of @entity15254 and @entity13839 siRNAs led to increased apoptosis in @entity899 mutant cells. CONCLUSIONS: Blocking autophagy has potential in the treatment of @entity694 by inducing apoptosis via @entity899 and ER stress, and suppressing the UPR pathway is a valid strategy to overcome resistance to autophagic inhibition.

Inhibition of autophagy exerts anti- @entity694 effects via apoptosis induced by XXXX activation and ER stress.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity15254 :: ('11793(Tax:10090)', 'Gene') :: ['Atg5'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity440 :: ('MESH:D013629', 'Chemical') :: ['tamoxifen'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity2985 :: ('MESH:D001397', 'Chemical') :: ['azoxymethane'] @entity899 :: ('22060(Tax:10090)', 'Gene') :: ['p53'] @entity2397 :: ('MESH:C012036', 'Chemical') :: ['sodium sulfate'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity25634 :: ('16669(Tax:10090)', 'Gene') :: ['K19', 'CK19'] @entity694 :: ('MESH:D003110', 'Disease') :: ['Colon tumors', 'colon tumors', 'colon cancer'] @entity13839 :: ('14828(Tax:10090)', 'Gene') :: ['BiP', 'immunoglobulin heavy-chain binding protein']
@entity899 :: (22060(Tax:10090),Gene) :: ['p53']
