Open Accessc‐Src inhibitor selectively inhibits triple‐negative breast cancer overexpressed Vimentin in vitro and in vivo
Author(s) -
Lou Longquan,
Yu Ziyi,
Wang Yue,
Wang Shui,
Zhao Yi
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13572
Subject(s) - vimentin , triple negative breast cancer , cancer research , proto oncogene tyrosine protein kinase src , epithelial–mesenchymal transition , oncogene , chemistry , biology , cell migration , cell , cancer , breast cancer , phosphorylation , cell cycle , microbiology and biotechnology , medicine , metastasis , immunology , immunohistochemistry , biochemistry
Oncogene c‐Src has been found to be a potential target for the treatment of triple‐negative breast cancer ( TNBC ). However, the therapeutic effects of the c‐Src inhibitor on TNBC patients are controversial compared to those on cell lines. The molecular mechanisms of the inhibitory effects of the c‐Src inhibitor on TNBC remain unclear. Herein, we showed that a specific c‐Src inhibitor, PP 2, was effective in inhibiting phosphorylation of c‐Src in 4 cell lines: T‐47D, SK ‐ BR ‐3, SUM 1315 MO 2, and MDA ‐ MB ‐231, regardless of hormone receptors and human epidermal growth factor receptor 2 ( HER 2) expression levels. Giving PP 2 preferentially reduced the S phase of cell cycles and inhibited colony formation in SUM 1315 MO 2 and MDA ‐ MB ‐231, but not in SK ‐ BR ‐3 and T‐47D cells. Furthermore, PP 2 effectively blocked cell migration/invasion and epithelial‐mesenchymal transition ( EMT ) in TNBC cell lines, SUM 1315 MO 2 and MDA ‐ MB ‐231. An EMT biomarker, vimentin, was highly expressed in 2 TNBC cell lines when they were compared with SK ‐ BR ‐3 and T‐47D cells. Further depletion of vimentin by sh RNA remarkably attenuated the inhibitory effects of the c‐Src inhibitor on TNBC cells in vitro and in vivo, indicating a crucial action of vimentin to affect the function of c‐Src in TNBC . This study provides an important rationale for the clinic to precisely select TNBC patients who would benefit from c‐Src inhibitor treatment. This finding suggests that traditional markers for TNBC are not sufficient to precisely define this aggressive type of cancer. Vimentin is identified as an important biomarker to enable categorization of TNBC .