Supporting a role for the GTPase Rab7 in prostate cancer progression.
Supporting a role for the GTPase Rab7 in prostate cancer progression.
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DOI：
10.1371/journal.pone.0087882
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cardelli JA
中科院分区：
文献类型：
--
作者：
Steffan JJ;Dykes SS;Coleman DT;Adams LK;Rogers D;Carroll JL;Williams BJ;Cardelli JA
侵袭和随后的转移是包括前列腺癌在内的大多数癌症的主要死亡原因。在此，我们报道了Rab7的潜在的肿瘤抑制特性，Rab7是一种调节溶酶体运输的GTP酶。溶酶体对环境信号的响应移动到细胞表面，增加了蛋白水解酶的分泌和细胞的侵袭。我们确定，曲格列酮和噻唑烷二酮家族的其他成员通过Rab7依赖的机制抑制细胞表面定向的溶酶体运输和组织蛋白酶B的分泌。此外，在体外和体内实验表明，表达Rab7shRNA的细胞具有更强的侵袭性。侵袭力的增加伴随着c-Met受体表达的增加和下游信号的延长，从而支持Rab7作为信号下调的媒介的作用。综上所述，这些结果表明，Rab7作为前列腺癌生长和侵袭的负调控因子，为其作为肿瘤抑制因子的潜力提供了进一步的证据。
Invasion and subsequent metastasis is the major cause of death from most cancers including prostate cancer. Herein we report on the potential tumor suppressive properties of Rab7, a GTPase that regulates trafficking of lysosomes. The movement of lysosomes to the cell surface in response to environmental cues increases the secretion of proteinases and cell invasion. We determined that Troglitazone and other members of the Thiazolidinedione family inhibit cell-surface directed lysosome trafficking and cathepsin B secretion through a Rab7-dependent mechanism. Moreover, Rab7 shRNA expressing cells were found to be more invasive in vitro and in vivo. Increased invasiveness was accompanied by elevated expression of the c-Met receptor and prolonged downstream signaling, thereby supporting a role for Rab7 as a mediator of signaling down-regulation. Taken together, these results suggested that Rab7 acts as a negative regulator of prostate tumor growth and invasion, providing further evidence for its potential as a tumor suppressor.
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