β-Catenin-dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells.

ABSTRACT: The Wnt/β-catenin pathway is constitutively activated in more than 90% of human colorectal cancer. Activated β-catenin stimulates cell proliferation and survival, however, its antiapoptotic mechanisms are not fully understood. We show here that activated β-catenin is required to suppress caspase-8 activation, but only in colon cancer cells that are resistant to tumor necrosis factor-α (TNF)-induced apoptosis. We found that lysosomal delivery of internalized TNF occurred at a faster pace in apoptosis-resistant than in apoptosis-sensitive colon cancer cells. Retardation of endosomal trafficking through vacuolar ATPase (V-ATPase) inhibition enhanced caspase-8 activation in apoptosis-resistant but not apoptosis-sensitive cells. Interestingly, knockdown of β-catenin also prolonged TNF associati

SUBMITTER: Han J 

PROVIDER: S-EPMC3571869 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature