MARCKS promotes invasion and is associated with biochemical recurrence in prostate cancer.
MARCKS promotes invasion and is associated with biochemical recurrence in prostate cancer.
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DOI：
10.18632/oncotarget.18894
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发表时间：
2017-09-22
期刊：
影响因子：
--
通讯作者：
Watson RW
中科院分区：
文献类型：
--
作者：
Dorris E;O'Neill A;Hanrahan K;Treacy A;Watson RW
低级别前列腺癌的过度治疗是临床医生和患者都认识到的问题。然而，对于那些可能受益的人来说，治疗不足有可能错过治愈的机会。需要识别疾病进展的新生物标志物，包括转移，以更好地对这些患者进行分层和适当的治疗。预测前列腺癌是否会复发是一个重要的临床问题，将影响患者的治疗选择。对其他癌症的研究已经将Marcks与转移联系起来。来自一组生化复发和非生化复发肿瘤的局部前列腺切除样本的组织微阵列被检测Marcks蛋白的表达。将靶向Marcks的siRNA导入前列腺癌细胞系，检测细胞的迁移、侵袭、增殖、存活和凋亡的功能终点。用荧光显微镜观察肌动蛋白，并检测钙粘附素开关和AKT通路激活的证据。与非生化复发患者相比，生化复发患者MARCKS表达上调。MARCKS基因敲除减少了前列腺癌细胞的迁移和侵袭，减少了MMP9mRNA的表达，并减少了细胞扩散，增加了前列腺癌细胞克隆中的细胞：细胞黏附。MARCKS基因敲除对前列腺癌细胞的增殖、活力和凋亡无影响。总而言之，Marcks促进迁移和侵袭，并与局部前列腺癌肿瘤的生化复发有关。发生这种情况的机制尚未完全阐明，但缺乏钙粘附素开关表明它不是通过上皮到间充质的转变。肌动蛋白重排表明Marcks通过调节细胞的结构促进侵袭。
Overtreatment of low-grade prostate cancer is a recognised problem for clinicians and patients. However, under-treatment runs the risk of missing the opportunity for cure in those who could benefit. Identification of new biomarkers of disease progression, including metastases, is required to better stratify and appropriately treat these patients. The ability to predict if prostate cancer will recur is an important clinical question that would impact treatment options for patients. Studies in other cancers have associated MARCKS with metastasis. Tissue microarrays of local prostatectomy samples from a cohort of biochemical recurrent and non-biochemical recurrent tumours were assayed for MARCKS protein expression. Prostate cancer cell lines were transfected with siRNA targeting MARCKS or a control and functional endpoints of migration, invasion, proliferation, viability and apoptosis were measured. Actin was visualised by fluorescent microscopy and evidence of a cadherin switch and activation of the AKT pathway were assayed. MARCKS was upregulated in biochemical recurrent patients compared to non-biochemical recurrent. Knockdown of MARCKS reduced migration and invasion of prostate cancer cells, reduced MMP9 mRNA expression, as well as decreasing cell spreading and increased cell:cell adhesion in prostate cancer cell colonies. Knockdown of MARCKS had no effect on proliferation, viability or apoptosis of the prostate cancer cells. In conclusion, MARCKS promotes migration and invasion and is associated with biochemical recurrence in localised prostate cancer tumours. The mechanisms by which this occurs have yet to be fully elucidated but lack of a cadherin switch indicates it is not via epithelial-to-mesenchymal transition. Actin rearrangement indicates that MARCKS promotes invasion through regulating the architecture of the cell.
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影响因子：
8
作者：
Bickeboeller, M.;Tagscherer, K. E.;Blaeker, H.
通讯作者：
Blaeker, H.
DOI：
10.1093/jnci/djg043
发表时间：
2003-09-17
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
D'Amico, AV;Moul, JW;Chen, MH
通讯作者：
Chen, MH
影响因子：
11.2
作者：
Graham, Tisheeka R.;Zhau, Haiyen E.;O'Regan, Ruth M.
通讯作者：
O'Regan, Ruth M.
影响因子：
4.7
作者：
Brooks, G;Brooks, SF;Goss, MW
通讯作者：
Goss, MW
DOI：
10.1038/nrm3758
发表时间：
2014-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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