Knockdown of flotillin-2 impairs the proliferation of breast cancer cells through modulation of Akt/FOXO signaling.

Abstract	Lipid rafts, specialized domains in cell membranes, function as physical platforms for various molecules to coordinate a variety of signal transduction processes. Flotillin-2 (FLOT2), a marker of lipid rafts, is involved in the progression of cancer, yet the precise mechanism remains unclear. In the present study, we examined the effect of FLOT2 on cell proliferation and found that silencing endogenous FLOT2 with shRNAs inhibited proliferation of breast cancer cells. Furthermore, the antiproliferative effect of silencing FLOT2 on breast cancer cells was associated with upregulation of cyclin-dependent kinase (CDK) inhibitors p21Cip1 and p27Kip1. Moreover, we further demonstrated that the silencing of FLOT2 enhanced the transcriptional activity of FOXO factors by decreasing its phosphorylation through inhibiting the PI3K/Akt signaling pathway. Taken together, our results provide the ﬁrst demonstration of a novel mechanism by which FLOT2 induces proliferation of breast cancer cells, and our ﬁndings suggest that FLOT2 plays an important role in oncogenesis of breast cancer and thereby may be a potential target for human breast cancer treatment.
Authors	Gui'e Xie, Jinlong Li, Jingsong Chen, Xuewei Tang, Shaoqing Wu, Can Liao
Journal	Oncology reports (Oncol Rep) Vol. 33 Issue 5 Pg. 2285-90 (May 2015) ISSN: 1791-2431 [Electronic] Greece
PMID	25738752 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cell Cycle Proteins FOXO1 protein, human FOXO3 protein, human FOXO4 protein, human Forkhead Box Protein O1 Forkhead Box Protein O3 Forkhead Transcription Factors Membrane Proteins Transcription Factors flotillins Proto-Oncogene Proteins c-akt
Topics	Adenocarcinoma (genetics) Breast Neoplasms (genetics) Cell Cycle Proteins Cell Line, Tumor Cell Proliferation (genetics) Forkhead Box Protein O1 Forkhead Box Protein O3 Forkhead Transcription Factors (genetics) Gene Knockdown Techniques Humans MCF-7 Cells Membrane Proteins (genetics) Phosphatidylinositol 3-Kinases (metabolism) Phosphorylation Proto-Oncogene Proteins c-akt (metabolism) Signal Transduction Transcription Factors (genetics)

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