Overexpression of β1 integrin contributes to polarity reversal and a poor prognosis of breast invasive micropapillary carcinoma
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Bingbing Liu1,2,3,*, Xia Zheng1,2,*, Fanfan Meng1,2, Yunwei Han1,2, Yawen Song1,2, Fangfang Liu1,2, Shuai Li1,2, Lanjing Zhang1,2,4,5,6,7, Feng Gu1,2, Xinmin Zhang8 and Li Fu1,2
1Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
2Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China
3Department of Pathology, Third Central Hospital of Tianjin, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry,Tianjin, China
4Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ, USA
5Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
6Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA
7Department of Pathology, Robert Wood Johnson Medical School, and Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA
8Department of Pathology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ, USA
*These authors contributed equally to this work
Li Fu, email: [email protected]
Xinmin Zhang, email: [email protected]
Feng Gu, email: [email protected]
Keywords: invasive micropapillary carcinoma; polarity reversal; β1 integrin; metastasis; breast
Received: September 07, 2017 Accepted: November 17, 2017 Published: November 30, 2017
Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive breast cancer. Polarity reversal exemplified by cluster growth is hypothesized to contribute to the invasiveness and metastasis of IMPC. In this study, we demonstrate that levels of β1 integrin and Rac1 expression were greater in breast IMPC than in invasive breast carcinoma of no specific type and paraneoplastic benign breast tissue. We show that silencing β1 integrin expression using the β1 integrin inhibitor AIIB2 partially restored polarity in IMPC primary cell clusters and downregulated Rac1. Thus, overexpression of β1 integrin upregulates Rac1. Univariate analysis showed that overexpression of β1 integrin and Rac1 was associated with breast cancer cell polarity reversal, lymph node metastasis, and poor disease-free survival in IMPC patients. Multivariate analysis revealed that polarity reversal was an independent predictor of poor disease-free survival. These findings indicate that overexpression of β1 integrin and the resultant upregulation of Rac1 contribute to polarity reversal and metastasis of breast IMPC, and that β1 integrin and Rac1 could be potential prognostic biomarkers and targets for treatment of breast IMPC.
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