Primary cilia are lost in preinvasive and invasive prostate cancer.
Primary cilia are lost in preinvasive and invasive prostate cancer.
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DOI：
10.1371/journal.pone.0068521
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
McDermott KM
中科院分区：
文献类型：
--
作者：
Hassounah NB;Nagle R;Saboda K;Roe DJ;Dalkin BL;McDermott KM
前列腺癌是世界上第二大最常见的男性癌症。原发性纤毛在侵袭前和侵袭性前列腺癌中的作用尚不清楚。然而，纤毛表达减少已经在人类癌症中被观察到，包括胰腺癌、肾细胞癌、乳腺癌、胆管癌和黑色素瘤。本研究的目的是表征原发性纤毛在侵袭前和侵袭性前列腺癌中的表达，并探讨原发性纤毛与Wnt信号通路的相关性。对具有前列腺癌形成阶段代表性的人前列腺组织（正常前列腺、前列腺上皮内瘤变（PIN）和浸润性前列腺癌（包括神经周围浸润））进行纤毛蛋白染色。测定初级纤毛出现的频率。与正常相比，纤毛细胞在PIN、浸润性癌和神经周围浸润性病变中的百分比下降。纤毛长度也被测量来间接测试功能。在PIN、癌症和神经周围浸润病变中，纤毛较短，提示功能障碍。原生纤毛已被证明可以抑制Wnt通路。Wnt信号的增加与前列腺癌有关。因此，我们研究了正常前列腺、侵袭前前列腺癌和侵袭性前列腺癌中原发性纤毛缺失与Wnt信号增加之间的相关性。为了研究Wnt信号传导，我们对一系列组织切片进行了β-catenin染色，作为Wnt信号传导的测量。对核β-连环蛋白进行了分析，发现Wnt信号在正常前列腺、PIN、一部分浸润性癌症和神经周围浸润的非纤毛细胞中较高。我们的研究结果表明，纤毛在正常情况下抑制上皮细胞中的Wnt信号通路，纤毛丢失可能在某些前列腺癌中Wnt信号通路增加中起作用。这些结果表明纤毛在人类前列腺癌中功能失调，Wnt信号的增加发生在一部分癌症中。
Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Little is known about the role of primary cilia in preinvasive and invasive prostate cancer. However, reduced cilia expression has been observed in human cancers including pancreatic cancer, renal cell carcinoma, breast cancer, cholangiocarcinoma, and melanoma. The aim of this study was to characterize primary cilia expression in preinvasive and invasive human prostate cancer, and to investigate the correlation between primary cilia and the Wnt signaling pathway. Human prostate tissues representative of stages of prostate cancer formation (normal prostate, prostatic intraepithelial neoplasia (PIN), and invasive prostate cancer (including perineural invasion)) were stained for ciliary proteins. The frequency of primary cilia was determined. A decrease in the percentage of ciliated cells in PIN, invasive cancer and perineural invasion lesions was observed when compared to normal. Cilia lengths were also measured to indirectly test functionality. Cilia were shorter in PIN, cancer, and perineural invasion lesions, suggesting dysfunction. Primary cilia have been shown to suppress the Wnt pathway. Increased Wnt signaling has been implicated in prostate cancer. Therefore, we investigated a correlation between loss of primary cilia and increased Wnt signaling in normal prostate and in preinvasive and invasive prostate cancer. To investigate Wnt signaling in our cohort, serial tissue sections were stained for β-catenin as a measure of Wnt signaling. Nuclear β-catenin was analyzed and Wnt signaling was found to be higher in un-ciliated cells in the normal prostate, PIN, a subset of invasive cancers, and perineural invasion. Our results suggest that cilia normally function to suppress the Wnt signaling pathway in epithelial cells and that cilia loss may play a role in increased Wnt signaling in some prostate cancers. These results suggest that cilia are dysfunctional in human prostate cancer, and increase Wnt signaling occurs in a subset of cancers.
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影响因子：
8.8
作者：
Morita, N;Uemura, H;Tsumatani, K;Cho, M;Hirao, Y;Okajima, E;Konishi, N;Hiasa, Y
通讯作者：
Hiasa, Y
影响因子：
6.4
作者：
Horvath, LG;Henshall, SM;Sutherland, RL
通讯作者：
Sutherland, RL
DOI：
10.1158/1078-0432.ccr-08-1754
发表时间：
2009-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Morgan TM;Lange PH;Porter MP;Lin DW;Ellis WJ;Gallaher IS;Vessella RL
通讯作者：
Vessella RL
影响因子：
6.2
作者：
Chen, GP;Shukeir, N;Rabbani, SA
通讯作者：
Rabbani, SA
影响因子：
11.5
作者：
Assikis, VJ;Do, KA;McDonnell, TJ
通讯作者：
McDonnell, TJ