TY - JOUR
T1 - Survivin is a novel target of CD44-promoted breast tumor invasion
AU - Abdraboh, Mohamed E.
AU - Gaur, Rajiv L.
AU - Hollenbach, Andrew D.
AU - Sandquist, Dane
AU - Raj, Madhwa H.G.
AU - Ouhtit, Allal
N1 - Funding Information:
Supported by His Majesty Sultan Qaboos University Strategic Grant SR/MED/GNET/10/01 (A.O.) and by The Egyptian Government scholarship (M.E.A.).
PY - 2011/8
Y1 - 2011/8
N2 - The hyaluronan (HA) receptor CD44 plays an essential role in cellcell or cellextracellular matrix communications and is a bioactive signal transmitter. Although a number of studies have described the function of CD44 in breast cancer (BC) metastasis, the underlying mechanisms have yet to be determined. By using a validated tetracycline-off-regulated CD44 expression system in the MCF-7 cell line combined with microarray analysis, we identified survivin (SVV) as a potential downstream transcriptional target of CD44. To test the hypothesis that SVV underpins CD44-promoted BC cell invasion, we combined molecular and pharmacologic approaches and showed that CD44 induction increased SVV expression levels, which in turn promotes BC cell invasion. Further, clinical analysis of breast tissue samples showed that SVV expression patterns paralleled those of the standard form of CD44 during breast tumor progression. More interestingly, we identified the PI3K/E2F1 pathway as a potential molecular link between HA/CD44 activation and SVV transcription. In addition to identifying SVV as a target for HA/CD44 signaling, this investigation provides a better understanding of the molecular mechanisms that underpin the novel function of SVV in breast cancer metastasis.
AB - The hyaluronan (HA) receptor CD44 plays an essential role in cellcell or cellextracellular matrix communications and is a bioactive signal transmitter. Although a number of studies have described the function of CD44 in breast cancer (BC) metastasis, the underlying mechanisms have yet to be determined. By using a validated tetracycline-off-regulated CD44 expression system in the MCF-7 cell line combined with microarray analysis, we identified survivin (SVV) as a potential downstream transcriptional target of CD44. To test the hypothesis that SVV underpins CD44-promoted BC cell invasion, we combined molecular and pharmacologic approaches and showed that CD44 induction increased SVV expression levels, which in turn promotes BC cell invasion. Further, clinical analysis of breast tissue samples showed that SVV expression patterns paralleled those of the standard form of CD44 during breast tumor progression. More interestingly, we identified the PI3K/E2F1 pathway as a potential molecular link between HA/CD44 activation and SVV transcription. In addition to identifying SVV as a target for HA/CD44 signaling, this investigation provides a better understanding of the molecular mechanisms that underpin the novel function of SVV in breast cancer metastasis.
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U2 - 10.1016/j.ajpath.2011.04.042
DO - 10.1016/j.ajpath.2011.04.042
M3 - Article
C2 - 21718681
AN - SCOPUS:80052473361
SN - 0002-9440
VL - 179
SP - 555
EP - 563
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -
