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Tumor Biology

, Volume 36, Issue 7, pp 5415–5423 | Cite as

USP2 promotes cell migration and invasion in triple negative breast cancer cell lines

  • Qing Qu
  • Yan Mao
  • Gang Xiao
  • Xiaochun Fei
  • Jinglong Wang
  • Yuzi Zhang
  • Junjun Liu
  • Guangcun Cheng
  • Xiaosong Chen
  • Jianhua Wang
  • Kunwei Shen
Research Article

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.

Keywords

Triple negative breast cancer USP2 Metastasis MMP2 

Notes

Acknowledgments

We thank Dr. Guohong Hu from the Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, China, for providing LM2-4175, SCP2, SCP28, and SCP46 cell lines. Research in the authors’ laboratory is supported by the Scientific Research Project of Shanghai Municipal Health Bureau (20134Y039) and the National Natural Funding of China (81202087, 81172520, 81202088).

Conflicts of interest

None

Supplementary material

13277_2015_3207_MOESM1_ESM.docx (16 kb)
ESM 1 (DOCX 16 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Qing Qu
    • 1
  • Yan Mao
    • 2
  • Gang Xiao
    • 3
  • Xiaochun Fei
    • 4
  • Jinglong Wang
    • 3
  • Yuzi Zhang
    • 2
  • Junjun Liu
    • 2
  • Guangcun Cheng
    • 3
  • Xiaosong Chen
    • 2
  • Jianhua Wang
    • 3
  • Kunwei Shen
    • 2
  1. 1.Department of Oncology, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Comprehensive Breast Health Center, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  3. 3.Department of Biochemistry and Molecular & Cell BiologyShanghai Jiao Tong University School of MedicineShanghaiChina
  4. 4.Department of Pathology, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

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