Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.
Folliculin contributes to VHL tumor suppressing activity in renal cancer through regulation of autophagy.
复制标题
滤泡素通过调节自噬有助于肾癌中 VHL 肿瘤抑制活性。
DOI：
10.1371/journal.pone.0070030
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Czyzyk-Krzeska MF
中科院分区：
文献类型：
--
作者：
Bastola P;Stratton Y;Kellner E;Mikhaylova O;Yi Y;Sartor MA;Medvedovic M;Biesiada J;Meller J;Czyzyk-Krzeska MF
Von Hippel-Lindau肿瘤抑制因子（VHL）在大多数透明细胞肾细胞癌（ccRCC）中丢失。滤泡蛋白（FLCN）是一种肿瘤抑制因子，其功能在Birt-Hogg-Dubé综合征（BHD）中丧失，BHD是一种以多种组织学类型的肾癌为特征的疾病，包括透明细胞癌、皮肤纤维滤泡瘤和气胸。本研究旨在探讨肾透明细胞癌细胞系和肿瘤中VHL和FLCN之间是否存在联系。我们证明VHL在RCC细胞系中在mRNA和蛋白水平上调节FLCN的表达，并且与匹配的正常肾组织相比，在VHL损失的人ccRCC肿瘤中FLCN蛋白表达降低。FLCN的敲低导致具有野生型VHL的RCC细胞在裸鼠原位异种移植物中的肿瘤形成增加，这表明FLCN在VHL的肿瘤抑制活性中起作用。有趣的是，FLCN，类似于VHL，是LC 3C介导的自噬程序的活性所必需的，我们以前已经表征为有助于VHL的肿瘤抑制活性。结果表明，肾癌中两种主要肿瘤抑制因子VHL和FLCN之间存在功能串扰，集中在自噬的调节上。
Von Hippel-Lindau tumor suppressor (VHL) is lost in the majority of clear cell renal cell carcinomas (ccRCC). Folliculin (FLCN) is a tumor suppressor whose function is lost in Birt-Hogg-Dubé syndrome (BHD), a disorder characterized by renal cancer of multiple histological types including clear cell carcinoma, cutaneous fibrofolliculoma, and pneumothorax. Here we explored whether there is connection between VHL and FLCN in clear cell renal carcinoma cell lines and tumors. We demonstrate that VHL regulates expression of FLCN at the mRNA and protein levels in RCC cell lines, and that FLCN protein expression is decreased in human ccRCC tumors with VHL loss, as compared with matched normal kidney tissue. Knockdown of FLCN results in increased formation of tumors by RCC cells with wild-type VHL in orthotopic xenografts in nude mice, an indication that FLCN plays a role in the tumor-suppressing activity of VHL. Interestingly, FLCN, similarly to VHL, is necessary for the activity of LC3C-mediated autophagic program that we have previously characterized as contributing to the tumor suppressing activity of VHL. The results show the existence of functional crosstalk between two major tumor suppressors in renal cancer, VHL and FLCN, converging on regulation of autophagy.
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影响因子：
8
作者：
Hartman, T. R.;Nicolas, E.;Klein-Szanto, A.;Al-Saleem, T.;Cash, T. P.;Simon, M. C.;Henske, E. P.
通讯作者：
Henske, E. P.
影响因子：
5.3
作者：
Mikhaylova, Olga;Ignacak, Monika L.;Czyzyk-Krzeska, Maria F.
通讯作者：
Czyzyk-Krzeska, Maria F.
影响因子：
5.3
作者：
Galbán, S;Martindale, JL;Gorospe, M
通讯作者：
Gorospe, M
影响因子：
5.8
作者：
Nookala RK;Langemeyer L;Pacitto A;Ochoa-Montaño B;Donaldson JC;Blaszczyk BK;Chirgadze DY;Barr FA;Bazan JF;Blundell TL
通讯作者：
Blundell TL
影响因子：
9.8
作者：
Schmidt, LS;Nickerson, ML;Linehan, WM
通讯作者：
Linehan, WM