title: YB-1 prevents apoptosis via the mTOR/STAT3 pathway in HER-2-overexpressing breast cancer cells.
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.
authors.affiliation: National Hospital Organization Kyushu Medical Cancer, Breast Care Center, Clinical Research Institute, Fukuoka, Japan. tfujii@qmed.hosp.go.jp
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Naoko
authors.initials: N
authors.lastname: Seki
authors.forename: Roka
authors.initials: R
authors.lastname: Namoto-Matsubayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Inoue
authors.forename: Uhi
authors.initials: U
authors.lastname: Toh
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu