Knockdown of flotillin-2 impairs the proliferation of breast cancer cells through modulation of Akt/FOXO signaling.
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.
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.
Gui'e
G
Xie
School of Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Jinlong
J
Li
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.
Jingsong
J
Chen
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.
Xuewei
X
Tang
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.
Shaoqing
S
Wu
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.
Can
C
Liao
D000230:Adenocarcinoma / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; C108803:FOXO4 protein, human; C106354:flotillins