cFLIP protein makes breast cancer cells resistant to TRAIL-induced apoptosis

December 12, 2015

The authors of this research proved that cFLIP plays a survival role in tumorous and non-tumorous breast epithelial cells, since the inhibition of its expression induces apoptosis. This type of apoptosis requires the formation of the death-inducing signalling complex, which includes TRAIL-R2 receptor, adapter molecule FADD and procaspase-8- but is TRAIL-independent itself.

Conversely, in the light of the cFLIP relevance in controlling apoptosis, researchers studied the role of cFLIP in breast epithelial cells MCF-10A morphogenesis -a process where apoptosis plays an essential role. Thus, cFLIPL/cFLIPS overexpression inhibits lumen formation in acini from breast epithelial cells when they are cultured in a 3D extracellular matrix  (3D cultures). Additionally, inhibition of cFLIP expression prevents the development of acini, since cells with low expression of cFLIP are unfeasible.

For this reason, regulation of cFLIP expression was very relevant to this research. Scientists determined that the PI3K/AKT signalling pathway is not the main responsible for cFLIP synthesis in breast cancer cell, but may be it is NF-kB pathway.

Additionally, this study revealed that the ubiquitin-proteasome system plays a key role in cFLIP cell degradation. At present, researchers are trying to identify E3-ubiquitin ligase protein, responsible for cFLIP degradation by such system.

Source: Andalusian Institute for Molecular Biology and Regenerative Medicine