Extracellular cleavage of the p75 neurotrophin receptor is implicated in its pro‐survival effect in breast cancer cells. Issue 16 (4th July 2013)

• Record Type: Journal Article
• Authors: Verbeke, Stéphanie; Tomellini, Elisa; Dhamani, Fatima; Meignan, Samuel; Adriaenssens, Eric; Xuefen, Le Bourhis
• Is Part Of: FEBS letters. Volume 587:Issue 16(2013)
• Page Start: 2591
• Page End: 2596
• Publication Date: 2013-07-04
• Subjects: FBS -- fetal bovine serum -- CTF -- carboxyl-terminal fragment -- ICD -- intracellular domain -- RIP -- regulated intramembrane proteolysis -- PS -- presenilin -- ADAM -- a disintegrin and metalloprotease -- TAPI -- tumor necrosis factor-α protease inhibitor -- TRAIL -- TNF-related apoptosis-inducing ligand -- p75NTR -- Regulated proteolysis -- Survival -- Breast cancer cell; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.06.039
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The p75 neurotrophin receptor (p75 NTR ) undergoes sequential proteolytic cleavages leading to the generation of a carboxyl‐terminal fragment (p75 NTR ‐CTF) and an intracellular domain (p75 NTR ‐ICD) in many cellular models. We have previously shown that p75 NTR is involved in the survival of breast cancer cells. Here, we demonstrated that p75 NTR cleavage occurs also in these cells. Surprisingly, p75 NTR ‐CTF increased cell survival, whereas p75 NTR ‐ICD had no effect. The pro‐survival effect of p75 NTR ‐CTF was associated with a decrease of TNF‐related apoptosis‐inducing ligand (TRAIL)‐induced PARP and caspase 3 cleavages. Finally, our findings indicate that p75 NTR could favor cell survival via its carboxyl‐terminal fragment, independently of PI3‐kinase, NF‐κB, or MAP kinase signaling pathways. Abstract : The p75 neurotrophin receptor (p75 NTR ) undergoes sequential proteolytic cleavages in MDA‐MB‐231breast cancer cells. The carboxyl‐terminal fragment (p75 NTR ‐CTF) but not the intracellular domain (p75 NTR ‐ICD) is able to promote cell survival. p75 NTR ‐CTF favors cell survival independently of PI3‐kinase, NF‐κB, or MAP kinase signaling pathways.