Resistance to apoptosis is a recurrent theme in @entity694 . We have shown previously that the 7-transmembrane spanning receptor @entity14610 for orexins promotes robust apoptosis in the @entity1 @entity694 cell line HT29 through an entirely novel mechanism involving phosphorylation of @entity669 -based motifs in @entity14610 . Here, we investigated the status of @entity14610 in a large series of @entity1 @entity14 and hepatic metastases. All primary @entity14 regardless of their localization and Duke's stages and all hepatic metastases tested expressed @entity14610 mRNA and/or protein. In sharp contrast, adjacent normal colonocytes or hepatocytes as well as control normal tissues were negative. Next, we showed that nine @entity1 @entity694 cell lines established from @entity5 or metastases expressed @entity14610 mRNA and underwent important apoptosis on @entity24068 challenge. Most interestingly, @entity24068 also promoted robust apoptosis in cells that are resistant to the most commonly used drug in @entity694 chemotherapy, @entity1487 . When @entity1 @entity694 cells were xenografted in @entity19 , @entity24068 administered at day 0 strongly slowed the @entity5 growth and even reversed the development of @entity5 when administered 7 days after cell inoculation. @entity24068 also acts by promoting @entity5 apoptosis in vivo because @entity185 is activated in @entity5 on orexin treatment of @entity19 . These findings support that @entity14610 is an Achilles heel of @entity694 , even after @entity3 or chemoresistance. They suggest that @entity14610 agonists might be novel candidates for @entity694 therapy.

Aberrant expression of OX1 receptors for orexins in XXXX and liver metastases: an openable gate to apoptosis.

@entity1 :: ('9606', 'Species') :: ['human'] @entity5 :: ('MESH:D009369', 'Disease') :: ['established tumors', 'tumor', 'primary tumors', 'tumors'] @entity24068 :: ('15171(Tax:10090)', 'Gene') :: ['orexin-A', 'Orexin-A'] @entity19 :: ('10090', 'Species') :: ['nude mice'] @entity185 :: ('12367(Tax:10090)', 'Gene') :: ['caspase-3'] @entity14610 :: ('3061', 'Gene') :: ['OX1R'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal tumors'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon cancer', 'colon cancers'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5-fluorouracil']
@entity694 :: (MESH:D003110,Disease) :: ['colon cancers']
