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Sorcin silencing inhibits epithelial-to-mesenchymal transition and suppresses breast cancer metastasis in vivo

Authors
  • Hu, Yunhui1, 2, 3
  • Li, Shuangjing1, 4
  • Yang, Ming1
  • Yan, Cihui1
  • Fan, Dongmei1
  • Zhou, Yuan1
  • Zhang, Yanjun1
  • Yagüe, Ernesto2
  • Xiong, Dongsheng1
  • 1 Chinese Academy of Medical Sciences & Peking Union Medical College, State Key Laboratory of Experimental Hematology, Department of Pharmacy, Institute of Hematology & Hospital of Blood Diseases, Tianjin, 300020, China , Tianjin (China)
  • 2 Imperial College London, Hammersmith Hospital Campus, Division of Cancer, Du Cane Road, London, W12 0NN, UK , London (United Kingdom)
  • 3 Tianjin Medical University Cancer Institute and Hospital, Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin, 300020, China , Tianjin (China)
  • 4 Liaocheng People’s Hospital, Liaocheng, Shandong, 252000, China , Liaocheng (China)
Type
Published Article
Journal
Breast Cancer Research and Treatment
Publisher
Springer-Verlag
Publication Date
Dec 15, 2013
Volume
143
Issue
2
Pages
287–299
Identifiers
DOI: 10.1007/s10549-013-2809-2
Source
Springer Nature
Keywords
License
Yellow

Abstract

Sorcin, a 22-kDa calcium-binding protein, renders cancer cells resistant to chemotherapeutic agents, thus playing an important role in multidrug resistance. As there is a clear association between drug resistance and an aggressive phenotype, we asked whether sorcin affects also the motility, invasion, and stem cell characteristics of cancer cells. We have used both RNA interference (transient and stable expression of hairpins) and a lentiviral expression vector to experimentally modulate sorcin expression in a variety of cells. We demonstrate that sorcin depletion in MDA-MB-231 breast cancer cells reduces the pool of CD44+/CD24− and ALDH1high cancer stem cells (CSCs) as well as mammosphere-forming capacity. We also observe that sorcin regulates epithelial-mesenchymal transition and CSCs partly through E-cadherin and vascular endothelial growth factor expression. This leads to the acquisition of an epithelial-like phenotype, attenuating epithelial-mesenchymal transition and suppression of metastases in nude mice. The sorcin-depleted phenotype can also be reproduced in lung adenocarcinoma A549 cells and lung fibrosarcoma HT1080 cells. In addition, overexpression of sorcin in MCF7 cells, which have low endogenous sorcin expression levels, increases their migration and invasion in vitro. This offers the rationale for the development of therapeutic strategies down-regulating sorcin expression for the treatment of cancer.

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