Protein tyrosine phosphatase receptor-type δ acts as a negative regulator suppressing breast cancer

// Xiaotang Yu 1, * , Fan Zhang 2, * , Jun Mao 1 , Ying Lu 1 , Jiazhi Li 1 , Wei Ma 3 , Shujun Fan 1 , Chunying Zhang 1 , Qing Li 1 , Bo Wang 1 , Bo Song 1 and Lianhong Li 1 1 Department of Pathology and Forensic Medicine, Dalian Medical University, Dalian 116044, PR China 2 Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116044, PR China 3 Department of Human Anatomy, Dalian Medical University, Dalian 116044, PR China * These authors have contributed equally to this work Correspondence to: Lianhong Li, email: lilianhong917@126.com Keywords: protein tyrosine phosphatase receptor-type δ, signal transducer and activator of transcription 3, breast cancer stem cells, epithelial-mesenchymal transition, interleukin-6 Received: February 15, 2017      Accepted: October 03, 2017      Published: October 24, 2017 ABSTRACT Protein tyrosine phosphatase receptor-type δ (PTPRD) is frequently inactivated in human cancers. This study investigated the role of PTPRD in the regulation of stemness, epithelial-mesenchymal transition (EMT), and migration and invasion in breast cancer cells. In vitro , PTPRD silencing using siRNA enhanced the stem cell-like properties of breast cancer cells, including their mammosphere- and holoclone-forming abilities, and it promoted tumorigenicity in vivo . PTPRD knockdown also increased the CD44 + /CD24 − breast cancer stem cell (BCSC) population and the expression of the stem cell markers ALDH1 and OCT4. It also promoted migration and invasion by breast cancer cell, EMT, and activation of signal transducer and activator of transcription 3 (STAT3). BCSCs expressed low levels of PTPRD, displayed mesenchymal phenotypes, and were more sensitive to IL-6-mediated STAT3 activation than non-BCSCs. PTPRD expression was upregulated by IL-6 in breast cancer cells, thereby establishing a negative feedback circuit by which IL-6 induced canonical STAT3 phosphorylation and transiently upregulated PTPRD, which in turn dephosphorylated STAT3 and prevented downstream signaling via the IL-6/STAT3 cascade. These data suggest that therapies aimed at restoring or enhancing PTPRD expression may be effective in controlling breast cancer progression and metastasis.