HDAC3 impacts multiple oncogenic pathways in colon cancer cells with effects on Wnt and vitamin D signaling

Godman, Cassandra A.; Joshi, Rashmi A; Tierney, Brendan R.; Greenspan, Emily J.; Rasmussen, Theodore P.; Wang, Hsin-Wei; Shin, Dong-Guk; Rosenberg, Daniel W.; Giardina, Charles

doi:10.4161/cbt.7.10.6561

Cited by 80 publications

(62 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results suggest that the effect of HDAC3 on the WWOX-RUNX2 interaction should be studied. It has been reported that HDAC3 affects the Wnt/b-catenin pathway in colon cancer cells through an undefined mechanism (18). Consistent with this observation, we found that HDAC3 strongly inhibits the transcriptional activity of b-catenin.…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the β-Catenin Coactivator BCL9-2 in Breast Cancer Cells

El-Hage

Petitalot

Monsoro-Burq

et al. 2015

Molecular Cancer Research

View full text Add to dashboard Cite

The WW domain containing oxidoreductase (WWOX) has recently been shown to inhibit of the Wnt/b-catenin pathway by preventing the nuclear import of disheveled 2 (DVL2) in human breast cancer cells. Here, it is revealed that WWOX also interacts with the BCL9-2, a cofactor of the Wnt/b-catenin pathway, to enhance the activity of the b-catenin-TCF/LEF (T-cell factor/ lymphoid enhancer factors family) transcription factor complexes. By using both a luciferase assay in MCF-7 cells and a Xenopus secondary axis induction assay, it was demonstrated that WWOX inhibits the BCL9-2 function in Wnt/b-catenin signaling. WWOX does not affect the BCL9-2-b-catenin association and colocalizes with BCL9-2 and b-catenin in the nucleus of the MCF-7 cells. Moreover, WWOX inhibits the b-catenin-TCF1 interaction. Further examination found that HDAC3 associates with BCL9-2, enhances the inhibitory effect of WWOX on BCL9-2 transcriptional activity, and promotes the WWOX-BCL9-2 interaction, independent of its deacetylase activity. However, WWOX does not influence the HDAC3-BCL9-2 interaction. Altogether, these results strongly indicate that nuclear WWOX interacts with BCL9-2 associated with b-catenin only when BCL9-2 is in complex with HDAC3 and inhibits its transcriptional activity, in part, by inhibiting the b-catenin-TCF1 interaction. The promotion of the WWOX-BCL9-2 interaction by HDAC3, independent of its deacetylase activity, represents a new mechanism by which this HDAC inhibits transcription. Implications:The inhibition of the transcriptional activity of BCL9-2 by WWOX and HDAC3 constitutes a new molecular mechanism and provides new insight for a broad range of cancers.

show abstract

Section: Discussionsupporting

confidence: 80%

“…Class 1 HDACs (HDAC1, 2, 3, and 8) are nuclear Zndependent enzymes. HDAC1, 2, and 3 are negative regulators of the Wnt/b-catenin signaling (16)(17)(18). The corepressors Groucho/TLE proteins inhibit the Wnt/b-catenin pathway transcriptional activity by competing with b-catenin for Tcl/Lef factors binding (19).…”

Section: Introductionmentioning

confidence: 99%

The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the β-Catenin Coactivator BCL9-2 in Breast Cancer Cells

El-Hage

Petitalot

Monsoro-Burq

et al. 2015

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…RIPA buffer was employed for protein extraction and 30 μg of protein was denatured under reducing conditions. 49,73 Proteins were separated on 4-20% gradient gels (Bio-Rad) and transferred to nitrocellulose by voltage gradient transfer. The resulting blots were blocked with 5% (w/v) non-fat dry milk in PBS + 0.1% (v/v) Tween-20.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands

Chopra

Kuratnik

Scocchera

et al. 2013

Cancer Biology & Therapy

Self Cite

View full text Add to dashboard Cite

“…20 g of protein was denatured under reducing conditions (27,28), separated on 4 -20% gradient gels (BioRad), and transferred to nitrocellulose by voltage gradient transfer. The resulting blots were blocked with 5% (w/v) nonfat dry milk in PBS ϩ 0.1% (v/v) Tween 20.…”

Section: Methodsmentioning

confidence: 99%

Novel Piperazine-based Compounds Inhibit Microtubule Dynamics and Sensitize Colon Cancer Cells to Tumor Necrosis Factor-induced Apoptosis

Chopra

Anderson

Giardina

2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Mitotic spindles are important targets of cancer chemotherapeutic agents. Results: A new class of tubulin-targeting agents is identified that effectively sensitizes colon cancer cells to ligand-induced apoptosis. Conclusion: AK301 is a novel, piperazine-based compound that induces mitotic arrest and increases ligand-dependent apoptosis. Significance: Mitotically active compounds that stimulate ligand-induced apoptotic signaling might be useful for augmenting immune-based cancer therapies.

show abstract

HDAC3 impacts multiple oncogenic pathways in colon cancer cells with effects on Wnt and vitamin D signaling

Cited by 80 publications

References 65 publications

The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the β-Catenin Coactivator BCL9-2 in Breast Cancer Cells

The Tumor-Suppressor WWOX and HDAC3 Inhibit the Transcriptional Activity of the β-Catenin Coactivator BCL9-2 in Breast Cancer Cells

Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands

Novel Piperazine-based Compounds Inhibit Microtubule Dynamics and Sensitize Colon Cancer Cells to Tumor Necrosis Factor-induced Apoptosis

Contact Info

Product

Resources

About