SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer.
SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer.
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DOI：
10.3389/fcell.2021.678967
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhao SC
中科院分区：
文献类型：
--
作者：
Xiao ZM;Lv DJ;Yu YZ;Wang C;Xie T;Wang T;Song XL;Zhao SC
SWI/SNF相关的、基质相关的、肌动蛋白依赖的染色质亚家族C成员调节因子1（SMARCC 1）蛋白是多种癌症中潜在的肿瘤抑制因子。然而，它在前列腺癌（PCa）中的作用仍然存在争议。本研究的目的是确定SMARCC 1在PCa中的生物学功能，并探讨其潜在的调控机制。通过免疫组化验证SMARCC 1在PCa组织中的表达。同时，通过功能实验研究SMARCC 1缺失对PCa细胞增殖和转移的调控作用。Western blotting检测相关蛋白的表达水平。我们的研究结果表明，SMARCC 1在前列腺癌中表达显著下调，Gleason评分（GS）高于低GS。SMARCC 1表达降低与GS增高及预后不良相关。此外，我们发现SMARCC 1的沉默通过促进细胞周期进程和通过诱导上皮间质转化（EMT）增强细胞迁移来显著加速细胞增殖。此外，SMARCC 1的消耗促进PCa异种移植物生长和鼠模型中的肺转移。从机制上讲，SMARCC 1的缺失激活了PCa细胞中的PI 3 K/AKT通路。SMARCC 1通过PI 3 K/AKT信号通路抑制PCa细胞增殖和转移，是一种新的治疗靶点。
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms. The expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting. Our finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells. SMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.
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DOI：
10.3109/00365599.2010.530295
发表时间：
2011-03-01
影响因子：
--
作者：
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通讯作者：
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