p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma

Miguel de La Cruz-Morcillo (1) , Julien Berger (1, 2) , Ricardo Sánchez-Prieto (3) , Sofiane Saada (1) , Thomas Naves (1) , Angélique Guillaudeau (4) , Aurélie Perraud (1) , Philippe Sindou (1) , Aurélie Lacroix (1) , Aurélien Descazeaud (2, 1) , Fabrice Lalloué (1) , Marie-Odile Jauberteau (1, 5)

1 HCP - Homéostasie Cellulaire et Pathologies
2 Service de Néphrologie, Dialyse, Transplantations [CHU Limoges]
3 UCLM - Universidad de Castilla-La Mancha = University of Castilla-La Mancha
4 Service d'Hématologie biologique [CHU Limoges]
5 Service d'Immunologie et immunogénétique [CHU Limoges]

p75NTR, a member of TNF receptor family, is the low affinity receptor common to several mature neurotrophins and the high affinity receptor for pro-neurotrophins. Brain-Derived Neurotrophic Factor (BDNF), a member of neurotrophin family has been described to play an important role in development and progression of several cancers, through its binding to a high affinity tyrosine kinase receptor B (TrkB) and/ or p75NTR. However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated. An overexpression of p75NTR, pro-BDNF, and to a lesser extent for TrkB and sortilin, was detected by immunohistochemistry in a cohort of 83 clear cell RCC tumors. p75NTR, mainly expressed in tumor tissues, was significantly associated with higher Fuhrman grade in multivariate analysis. In two derived-RCC lines, 786-O and ACHN cells, we demonstrated that pro-BDNF induced cell survival and migration, through p75NTR as provided by p75NTR RNA silencing or blocking antip75NTR antibody. This mechanism is independent of TrkB activation as demonstrated by k252a, a tyrosine kinase inhibitor for Trk neurotrophin receptors. Taken together these data highlight for the first time an important role for p75NTR in renal cancer and indicate a putative novel target therapy in RCC.

Mots clés: p75NTR; pro-BDNF; TrkB; sortilin; renal cell carcinoma

Domaines: Biologie cellulaire

Miguel de La Cruz-Morcillo, Julien Berger, Ricardo Sánchez-Prieto, Sofiane Saada, Thomas Naves, et al.. p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma. Oncotarget, 2016, 7 (23), pp.34480-97. ⟨10.18632/oncotarget.8911⟩. ⟨hal-01819217⟩