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

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 a...

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Autores principales: Han, Jinbo, Sridevi, Priya, Ramirez, Michael, Ludwig, Kirsten J., Wang, Jean Y. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571869/
https://www.ncbi.nlm.nih.gov/pubmed/23264463
http://dx.doi.org/10.1091/mbc.E12-09-0662
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author Han, Jinbo
Sridevi, Priya
Ramirez, Michael
Ludwig, Kirsten J.
Wang, Jean Y. J.
author_facet Han, Jinbo
Sridevi, Priya
Ramirez, Michael
Ludwig, Kirsten J.
Wang, Jean Y. J.
author_sort Han, Jinbo
collection PubMed
description 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 association with the early endosome and enhanced caspase-8 activation in apoptosis-resistant but not apoptosis-sensitive colon cancer cells. In a mouse model of inflammation-associated colon tumors, we found nuclear expression of β-catenin, resistance to TNF-induced apoptosis, and reactivation of apoptosis in vivo after cotreatment of TNF with a V-ATPase inhibitor. Together these results suggest that activated β-catenin can facilitate endosomal trafficking of internalized TNF to suppress caspase-8 activation in colon cancer cells.
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spelling pubmed-35718692013-04-30 β-Catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells Han, Jinbo Sridevi, Priya Ramirez, Michael Ludwig, Kirsten J. Wang, Jean Y. J. Mol Biol Cell Articles 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 association with the early endosome and enhanced caspase-8 activation in apoptosis-resistant but not apoptosis-sensitive colon cancer cells. In a mouse model of inflammation-associated colon tumors, we found nuclear expression of β-catenin, resistance to TNF-induced apoptosis, and reactivation of apoptosis in vivo after cotreatment of TNF with a V-ATPase inhibitor. Together these results suggest that activated β-catenin can facilitate endosomal trafficking of internalized TNF to suppress caspase-8 activation in colon cancer cells. The American Society for Cell Biology 2013-02-15 /pmc/articles/PMC3571869/ /pubmed/23264463 http://dx.doi.org/10.1091/mbc.E12-09-0662 Text en © 2013 Han et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Han, Jinbo
Sridevi, Priya
Ramirez, Michael
Ludwig, Kirsten J.
Wang, Jean Y. J.
β-Catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells
title β-Catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells
title_full β-Catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells
title_fullStr β-Catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells
title_full_unstemmed β-Catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells
title_short β-Catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells
title_sort β-catenin–dependent lysosomal targeting of internalized tumor necrosis factor-α suppresses caspase-8 activation in apoptosis-resistant colon cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571869/
https://www.ncbi.nlm.nih.gov/pubmed/23264463
http://dx.doi.org/10.1091/mbc.E12-09-0662
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