SSX2 regulates focal adhesion but does not drive the epithelial to mesenchymal transition in prostate cancer
SSX2 regulates focal adhesion but does not drive the epithelial to mesenchymal transition in prostate cancer
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DOI：
10.18632/oncotarget.9802
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发表时间：
2016-08-09
期刊：
影响因子：
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通讯作者：
McNeel, Douglas G.
中科院分区：
文献类型：
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作者：
Bloom, Jordan E.;McNeel, Douglas G.
前列腺癌是美国男性最常见的恶性肿瘤。转移性前列腺癌是这种疾病的致命形式，预期寿命约为五年。识别与这种转移性疾病相关的因素对未来的治疗至关重要。一个这样的因子是SSX基因家族，一个癌症/睾丸抗原（CTA）转录因子家族，其已被证明在其他癌症中异常表达并与上皮向间质转化（EMT）相关。我们先前已经表明，SSX在前列腺癌中的表达仅限于转移性组织，而不是原发性肿瘤。在这项研究中，我们已经确定SSX 2作为主要的SSX家族成员在前列腺癌中表达，并发现其表达在外周血中的19 54（35%）前列腺癌患者，表达仅限于循环肿瘤细胞，并在7 15（47%）转移性cDNA样本。此外，我们通过在前列腺癌细胞系中敲低和过表达来检查SSX 2在前列腺癌中的功能。虽然过表达对形态学或基因转录变化的影响很小，但SSX 2的敲低导致上皮形态学、细胞增殖增加、参与粘着斑的基因表达增加、锚定非依赖性生长减少、侵袭增加和体内致瘤性增加。我们从这些发现中得出结论，前列腺癌中的SSX 2表达不是EMT的驱动因素，但参与与EMT相关的过程，包括可能与肿瘤细胞播散相关的粘着斑丧失。
Prostate cancer is the most commonly diagnosed malignancy for men in the United States. Metastatic prostate cancer, the lethal form of the disease, has a life expectancy of approximately five years. Identification of factors associated with this transition to metastatic disease is crucial for future therapies. One such factor is the SSX gene family, a family of cancer/testis antigens (CTA) transcription factors which have been shown to be aberrantly expressed in other cancers and associated with the epithelial to mesenchymal transition (EMT). We have previously shown that SSX expression in prostate cancers was restricted to metastatic tissue and not primary tumors. In this study, we have identified SSX2 as the predominant SSX family member expressed in prostate cancer, and found its expression in the peripheral blood of 19 of 54 (35%) prostate cancer patients, with expression restricted to circulating tumor cells, and in 7 of 15 (47%) metastatic cDNA samples. Further, we examined SSX2 function in prostate cancer through knockdown and overexpression in prostate cancer cell lines. While overexpression had little effect on morphology or gene transcript changes, knockdown of SSX2 resulted in an epithelial morphology, increased cell proliferation, increased expression of genes involved in focal adhesion, decreased anchorage independent growth, increased invasion, and increased tumorigenicity in vivo. We conclude from these findings that SSX2 expression in prostate cancer is not a driver of EMT, but is involved in processes associated with EMT including loss of focal adhesion that may be related to tumor cell dissemination.