title: USP2 promotes cell migration and invasion in triple negative breast cancer cell lines.
abstract: 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® 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-MB-468 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.
authors: Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Qing
authors: Q
authors: Qu
authors: Yan
authors: Y
authors: Mao
authors: Gang
authors: G
authors: Xiao
authors: Xiaochun
authors: X
authors: Fei
authors: Jinglong
authors: J
authors: Wang
authors: Yuzi
authors: Y
authors: Zhang
authors: Junjun
authors: J
authors: Liu
authors: Guangcun
authors: G
authors: Cheng
authors: Xiaosong
authors: X
authors: Chen
authors: Jianhua
authors: J
authors: Wang
authors: Kunwei
authors: K
authors: Shen
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D018572:Disease-Free Survival; D010450:Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D043222:Ubiquitin Thiolesterase
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2