The roles of CUX1 homeodomain proteins in the establishment of a transcriptional program required for cell migration and invasion

Kedinger, Valérie; Nepveu, Alain

doi:10.4161/cam.4.3.11407

Cited by 16 publications

(18 citation statements)

References 36 publications

(42 reference statements)

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“…CUX1 is a transcription factor that regulates multiple processes including cell cycle progression, chromosomal segregation and cell migration 29,30 . Consistent with the effects of miR122 silencing described above, CUX1 was reported to modulate cell motility and invasion through the control of RhoA activity [31][32][33] . We observed that whereas CUX1 mRNA levels remained unchanged ( Fig.…”

Section: Establishment Of Mir122-silenced Hcc Cell Linessupporting

confidence: 74%

“…The underlying mechanisms for the role of CUX1 in cancer is complex and is likely to involve both cell-autonomous and non-cell autonomous effects. However, from cell-based assays it is clear that CUX1 has a role in at least three distinct processes: cell motility, cell cycle progression and chromosome segregation 30,31,36,48 . The knockdown of CUX1 using siRNA was shown to delay entry into S phase and to hinder cell motility and invasion 31,36,48 .…”

Section: Discussionmentioning

confidence: 99%

“…However, from cell-based assays it is clear that CUX1 has a role in at least three distinct processes: cell motility, cell cycle progression and chromosome segregation 30,31,36,48 . The knockdown of CUX1 using siRNA was shown to delay entry into S phase and to hinder cell motility and invasion 31,36,48 . In contrast, overexpression of p110 CUX1 was able to accelerate S phase entry and to stimulate proliferation, migration and invasion 35,48 .…”

Section: Discussionmentioning

confidence: 99%

“…This miR122/CUX1/miR214/ZBTB20/ AFP pathway may explain the deregulated AFP expression observed in HCC cells. Additionally, the ability of CUX1 to activate RhoA and to regulate the expression of many proteins involved in cell motility may explain the increased migration and invasiveness associated with malignancy of HCC [31][32][33][34][35][36] . It should be noted that, although this analysis revealed a trend toward inverse correlation between expression of miR122 and expression of AFP, this correlation could not be applied to all cases examined.…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma

et al. 2011

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α-fetoprotein (AFP) is not only a widely used biomarker in hepatocellular carcinoma (HCC) surveillance, but is also clinically recognized as linked with aggressive tumour behaviour. Here we show that deregulation of microRnA122, a liver-specific microRnA, is a cause of both AFP elevation and a more biologically aggressive phenotype in HCC. We identify CuX1, a direct target of microRnA122, as a common central mediator of these two effects. using liver tissues from transgenic mice in which microRnA122 is functionally silenced, an orthotopic xenograft tumour model, and human clinical samples, we further demonstrate that a microRnA122/ CuX1/microRnA214/ZBTB20 pathway regulates AFP expression. We also show that the microRnA122/CuX1/RhoA pathway regulates the aggressive characteristics of tumours. We conclude that microRnA122 and associated signalling proteins may represent viable therapeutic targets, and that serum AFP levels in HCC patients may be a surrogate marker for deregulated intracellular microRnA122 signalling pathways in HCC tissues.

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Section: Establishment Of Mir122-silenced Hcc Cell Linessupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA122 is a key regulator of α-fetoprotein expression and influences the aggressiveness of hepatocellular carcinoma

et al. 2011

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“…Many transcriptional targets and cellular functions of CUX1 readily suggest mechanisms by which increased p110 or p75 CUX1 expression might promote tumour development and progression, including acceleration of S phase entry 21,22,41,62,63 , stimulation of cell migration and invasion 13,42,[64][65][66] , resistance to apoptosis 14 , and promotion of bipolar mitosis in the presence of supernumerary centrosomes 19 (reviewed in REF. 67).…”

Section: Mechanisms Of Action In Cancermentioning

confidence: 99%