p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma.
p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma.
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DOI：
10.18632/oncotarget.8911
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Jauberteau MO
中科院分区：
文献类型：
--
作者：
De la Cruz-Morcillo MA;Berger J;Sánchez-Prieto R;Saada S;Naves T;Guillaudeau A;Perraud A;Sindou P;Lacroix A;Descazeaud A;Lalloué F;Jauberteau MO
p75 NTR是TNF受体家族的成员，是多种成熟神经营养因子的低亲和力受体和前神经营养因子的高亲和力受体。脑源性神经营养因子（Brain-Derived Neurotrophic Factor，BDNF）是神经营养因子家族的一员，通过与高亲和力酪氨酸激酶受体B（Trk B）和/或p75 NTR结合，在多种肿瘤的发生发展中发挥重要作用。然而，这两种受体在肾细胞癌（RCC）中的功能尚未得到研究。在83例透明细胞肾细胞癌中，通过免疫组化检测到p75 NTR、pro-BDNF以及TrkB和分拣蛋白的过表达。p75 NTR主要在肿瘤组织中表达，多因素分析显示p75 NTR与肿瘤的高Fuhrman分级显著相关。在两个衍生的RCC系，786-O和ACHN细胞中，我们证明了pro-BDNF通过p75 NTR RNA沉默或阻断抗p75 NTR抗体提供的p75 NTR诱导细胞存活和迁移。该机制不依赖于TrkB激活，如Trk神经营养因子受体的酪氨酸激酶抑制剂k252 a所证明的。总之，这些数据首次突出了p75 NTR在肾癌中的重要作用，并表明了RCC中公认的新靶向治疗。
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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影响因子：
9.8
作者：
Johnston AL;Lun X;Rahn JJ;Liacini A;Wang L;Hamilton MG;Parney IF;Hempstead BL;Robbins SM;Forsyth PA;Senger DL
通讯作者：
Senger DL
影响因子：
4.6
作者：
Khwaja, F;Djakiew, D
通讯作者：
Djakiew, D
影响因子：
4.4
作者：
Fauchais, Anne-Laure;Lalloue, Fabrice;Jauberteau, Marie-Odile
通讯作者：
Jauberteau, Marie-Odile
p75 神经营养素受体抑制胃癌的侵袭和转移。
影响因子：
5.2
作者：
Jin, Haifeng;Pan, Yanglin;Fan, Daiming
通讯作者：
Fan, Daiming
影响因子：
5.3
作者：
MIDDLEMAS, DS;LINDBERG, RA;HUNTER, T
通讯作者：
HUNTER, T