p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma
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Miguel A. De la Cruz-Morcillo1,*, Julien Berger1,2,*, Ricardo Sánchez-Prieto3, Sofiane Saada1, Thomas Naves1, Angélique Guillaudeau4, Aurélie Perraud1, Philippe Sindou1, Aurélie Lacroix1, Aurélien Descazeaud1,2, Fabrice Lalloué1, Marie-Odile Jauberteau1
1Limoges University, Equipe Accueil 3842, Cellular Homeostasis and Diseases, Faculty of Medicine, 87025 Limoges, Cedex, France
2Department of Urology, University Hospital Limoges, 87042 Limoges, Cedex, France
3PCTCLM/CRIB Unidad de Medicina Molecular Laboratorio de Oncología/Unidad de Biomedicina UCLM-CSIC, Universidad de Castilla la Mancha, 02006 Albacete, Spain
4Department of Pathology, University Hospital Limoges, 87042 Limoges, Cedex, France
*These authors have contributed equally to this work
Marie-Odile Jauberteau, email: firstname.lastname@example.org
Keywords: p75NTR, pro-BDNF, TrkB, sortilin, renal cell carcinoma
Received: October 07, 2015 Accepted: April 10, 2016 Published: April 22, 2016
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 anti-p75NTR 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.
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