Failed Apoptosis Enhances Melanoma Cancer Cell Aggressiveness.

Cell Reports
Kevin BerthenetGabriel Ichim

Abstract

Triggering apoptosis remains an efficient strategy to treat cancer. However, apoptosis is no longer a final destination since cancer cells can undergo partial apoptosis without dying. Recent evidence shows that partial mitochondrial permeabilization and non-lethal caspase activation occur under certain circumstances, although it remains unclear how failed apoptosis affects cancer cells. Using a cancer cell model to trigger non-lethal caspase activation, we find that melanoma cancer cells undergoing failed apoptosis have a particular transcriptomic signature associated with focal adhesions, transendothelial migration, and modifications of the actin cytoskeleton. In line with this, cancer cells surviving apoptosis gain migration and invasion properties in vitro and in vivo. We further demonstrate that failed apoptosis-associated gain in invasiveness is regulated by the c-Jun N-terminal kinase (JNK) pathway, whereas its RNA sequencing signature is found in metastatic melanoma. These findings advance our understanding of how cell death can both cure and promote cancer.

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Citations

Nov 13, 2020·The FEBS Journal·Camila Castillo FerrerGabriel Ichim
Nov 26, 2020·Molecular & Cellular Oncology·Kevin BerthenetGabriel Ichim
Jan 23, 2021·Cancers·Vanessa CastelliMichele d'Angelo
Mar 16, 2021·EMBO Molecular Medicine·Shan JiangBenjamin Gibert
Aug 8, 2021·Cancers·Victoria ZaitcevaBoris Zhivotovsky
Aug 28, 2021·International Journal of Molecular Sciences·Caitlin Hounsell, Yun Fan

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