Hyaluronan suppresses prostate tumor cell proliferation through diminished expression of N-cadherin and aberrant growth factor receptor signaling.
Hyaluronan suppresses prostate tumor cell proliferation through diminished expression of N-cadherin and aberrant growth factor receptor signaling.
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DOI：
10.1016/j.yexcr.2011.01.026
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发表时间：
2011-05-01
影响因子：
3.7
通讯作者：
Simpson, Melanie A.
中科院分区：
文献类型：
--
作者：
Bharadwaj, Alamelu G.;Goodrich, Nathaniel P.;McAtee, Caitlin O.;Haferbier, Katie;Oakley, Gregory G.;Wahl, James K., III;Simpson, Melanie A.
透明质酸（HA）的产生在功能上与前列腺肿瘤的发生和转移有关。我们之前使用过表达HA合成酶HAS 3或临床相关透明质酸酶Hyal 1的前列腺肿瘤细胞来表明过量的HA产生会抑制肿瘤生长，而HA转换会加速前列腺的自发转移。在这里，我们研究了负责HAS 3和Hyal 1对肿瘤细胞表型的影响的途径。细胞周期进程的详细表征显示，Hyal 1的表达加速同步后的细胞周期重新进入，而HAS 3单独延迟进入。Hyal 1表达细胞在生长因子刺激下维持ERK磷酸化的能力显著降低，细胞周期蛋白依赖性激酶抑制剂p21的表达也显著降低。相反，HAS 3表达细胞表现出延长ERK磷酸化和增加表达的p21和p27，在异步和同步文化。细胞周期调节蛋白的变化伴随着HA诱导的N-钙粘蛋白的抑制，而E-钙粘蛋白表达和β-连环蛋白表达和分布保持不变。我们的研究结果是一致的模型，其中过量的HA合成抑制细胞增殖，促进同型E-钙粘蛋白介导的细胞-细胞粘附，从而信号，以提高细胞周期抑制剂的表达和抑制G1期到S期的转变。
Hyaluronan (HA) production has been functionally implicated in prostate tumorigenesis and metastasis. We previously used prostate tumor cells overexpressing the HA synthesizing enzyme HAS3 or the clinically relevant hyaluronidase Hyal1 to show that excess HA production suppresses tumor growth, while HA turnover accelerates spontaneous metastasis from the prostate. Here, we examined pathways responsible for effects of HAS3 and Hyal1 on tumor cell phenotype. Detailed characterization of cell cycle progression revealed that expression of Hyal1 accelerated cell cycle re-entry following synchronization, whereas HAS3 alone delayed entry. Hyal1 expressing cells exhibited a significant reduction in their ability to sustain ERK phosphorylation upon stimulation by growth factors, and in their expression of the cyclin dependent kinase inhibitor p21. In contrast, HAS3 expressing cells showed prolonged ERK phosphorylation and increased expression of both p21 and p27, in asynchronous and synchronized cultures. Changes in cell cycle regulatory proteins were accompanied by HA-induced suppression of N-cadherin, while E-cadherin expression and β-catenin expression and distribution remained unchanged. Our results are consistent with a model in which excess HA synthesis suppresses cell proliferation by promoting homotypic E-cadherin mediated cell-cell adhesion, consequently signaling to elevate cell cycle inhibitor expression and suppress G1 to S phase transition.
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影响因子：
10.5
作者：
LaBaer, J;Garrett, MD;Harlow, E
通讯作者：
Harlow, E
DOI：
10.1083/jcb.200611058
发表时间：
2007-02-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kothapalli D;Zhao L;Hawthorne EA;Cheng Y;Lee E;Puré E;Assoian RK
通讯作者：
Assoian RK
影响因子：
6
作者：
Bharadwaj, Alamelu G.;Kovar, Joy L.;Simpson, Melanie A.
通讯作者：
Simpson, Melanie A.
影响因子：
6
作者：
Kovar, Joy L.;Johnson, Mark A.;Simpson, Melanie A.
通讯作者：
Simpson, Melanie A.
影响因子：
4.8
作者：
El Sheikh, SS;Domin, J;Lalani, EN
通讯作者：
Lalani, EN