USP2 promotes cell migration and invasion in triple negative breast cancer cell lines
USP2 promotes cell migration and invasion in triple negative breast cancer cell lines
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DOI：
10.1007/s13277-015-3207-7
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发表时间：
2015-07-01
期刊：
影响因子：
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通讯作者：
Shen, Kunwei
中科院分区：
文献类型：
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作者：
Qu, Qing;Mao, Yan;Shen, Kunwei
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，通常与预后不良相关。我们研究的目的是鉴定预测TNBC进展的生物标志物。对包括四个具有转移和六个没有转移的原发性TNBC乳腺组织样品进行Affyssin GeneChip（R）分析（人基因组U133）。泛素特异性蛋白酶2（USP 2）被确定为在转移组中上调的基因，并通过免疫组织化学分析其在121例原发性乳腺癌，13对正常组织和13对转移性病变中的表达。采用对数秩检验和考克斯回归风险模型进行生存分析。在USP 2沉默和USP 2过表达的乳腺癌细胞系中的基质胶迁移和侵袭测定用于研究USP 2的体外机制。在乳腺肿瘤中检测到USP 2的阳性免疫染色，并与雌激素受体（ER）和孕激素受体（PR）状态和TNBC亚型相关。与原发性乳腺癌相比，USP 2在远处转移病灶中过表达。生存分析表明，阳性USP 2是无病生存的不良预后因素。在LM 2 -4175和SCP 46细胞中，USP 2表达的沉默与基质金属蛋白酶-2（MMP 2）表达的下调相关，从而降低了迁移和侵袭，而在MDA-MB-468和MDA-MB-231细胞中，USP 2的过表达增强了迁移和侵袭，并上调了MMP 2的表达。目前的研究表明，USP 2表达与TNBC细胞系的侵袭性和乳腺癌患者的不良生存相关，并且可以作为TNBC的预后生物标志物和治疗靶点。
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with a poor prognosis. The aim of our study was to identify biomarkers predictive of TNBC progression. Primary TNBC breast tissue samples including four with metastasis and six without metastasis were subjected to Affymetrix GeneChip (R) analysis (human genome U133). Ubiquitin-specific protease 2 (USP2) was identified as an upregulated gene in the metastatic group, and its expression was analyzed by immunohistochemistry in 121 primary breast cancers, 13 paired normal tissues, and 13 paired metastatic lesions. Survival analysis was performed using the log-rank test and Cox regression hazard model. Matrigel migration and invasion assays in USP2-silenced and USP2-overexpressed breast cancer cell lines were used to investigate the mechanisms of USP2 in vitro. Positive immunostaining for USP2 was detected in breast tumors and was correlated with estrogen receptor (ER) and progesterone receptor (PR) statuses and TNBC subtype. USP2 was overexpressed in distant metastatic lesions compared with primary breast cancers. Survival analyses demonstrated that positive USP2 is a poor prognostic factor for disease-free survival. Silencing of USP2 expression decreased migration and invasion in LM2-4175 and SCP46 cells in association with the downregulation of matrix metalloproteinase-2 (MMP2) expression, whereas overexpression of USP2 in MDA-MB468 and MDA-MB-231 cells enhanced migration and invasion and upregulated the expression of MMP2. The present study showed that USP2 expression is associated with TNBC cell line's invasiveness and poor survival of breast cancer patients and may serve as a prognostic biomarker and therapeutic target for TNBC.