YB-1 prevents apoptosis via the mTOR/STAT3 pathway in HER-2-overexpressing breast cancer cells. (March 2009)

• Record Type: Journal Article
• Authors: Fujii, Teruhiko; Seki, Naoko; Namoto-Matsubayashi, Roka; Takahashi, Hiroki; Inoue, Yuka; Toh, Uhi; Kage, Masayoshi; Shirouzu, Kazuo
• Is Part Of: Future oncology. Volume 5:Number 2(2009)
• Page Start: 153
• Page End: 156
• Publication Date: 2009-03
• Subjects: Oncology -- Periodicals; 616.99405
• DOI: 10.2217/14796694.5.2.153
• Languages: English
• ISSNs: 1479-6694

Abstract

Evaluation of: Lee C, Dhillon J, Wang MY et al. : Targeting YB-1 in HER-2 overexpressing breast cancer cells induces apoptosis via the mTOR/STAT3 pathway and suppresses tumor growth in mice. Cancer Res. 68 (21), 8661––8666 (2008). The transcription factor Y-box binding protein (YB)-1 is highly expressed in breast cancer cells and is strongly linked with breast cancer patient prognosis. In this paper, siRNA knockdown of YB-1 was used to investigate breast cancer cell proliferation. Six breast cancer cell lines that either overexpress HER-2 or were triple negative demonstrated growth inhibition following YB-1 knockdown. In particular, YB-1 knockdown induced apoptosis in BT-474-m1 and Au565 cells. Knockdown of YB-1 also decreased phosphorylation of STAT3S727, ERK1/2T202/Y204, mTORS2448 and total mTOR expression. When STAT3 was knocked down by siSTAT3, apoptosis was induced and constitutively active phosphorylated STAT3 was found to rescue YB-1-induced apoptosis. Furthermore, YB-1 knockdown remarkably suppressed colony formation in a soft agar assay, while delayed tumor formation was observed in mice. YB-1 knockdown inhibited cell growth and it is thought to involve induction of apoptosis via the mTOR/STAT3 intracellular signaling pathway. YB-1 is a promising molecular target for HER-2-overexpressing or triple-negative breast cancer cells.