Caspase independent cleavages of TDP-43 generates 35kD fragment that cause apoptosis of breast cancer cells

Highlights: • A novel 35kD fragment of TDP-43 was found in MCF7, a breast cancer cells which is null in caspase-3. • Accumulation of 35kD fragment of TDP-43 is the exterminating factor for TDP-43 cytotoxicity in MCF7. • The 35kD fragment of TDP-43 may be served as a potential therapeutic target to cure breast cancer. Transactive response DNA-binding protein 43kD (TDP-43) is a major component of tau-negative and ubiquitin-positive inclusions that characterize ALS (amyotrophic lateral sclerosis) and FTLD (frontotemporal lobar degeneration). Due to its central role in neurodegenerative disease pathogenesis, most research recently has focused on its role associated with neurodegeneration disease, research on neuron and glial cell showed that pathological TDP-43 is associated with cell apoptosis which lead to loss of functional neurons and glial cells. However, little is known about its role on cancer cells, here we report a 35kD fragment of TDP-43 also plays a key role in apoptosis of breast cancer cells, and may be served as a potential therapeutic target to cure cancer.