Faculty Opinions recommendation of Oncogenic function of ATDC in pancreatic cancer through Wnt pathway activation and beta-catenin stabilization.

Author(s):  
Martin Fernandez-Zapico
Cancer Cell ◽  
2009 ◽  
Vol 15 (3) ◽  
pp. 207-219 ◽  
Author(s):  
Lidong Wang ◽  
David G. Heidt ◽  
Cheong J. Lee ◽  
Huibin Yang ◽  
Craig D. Logsdon ◽  
...  

2021 ◽  
Author(s):  
Sajjad Sharifi ◽  
Farzad Rahmani ◽  
Abolfazl Nosrati-Tirkani ◽  
Shima Mehrabadi ◽  
Hamid Fiuji ◽  
...  

Abstract Background : The Wnt/beta-catenin pathway is dysregulated in pancreatic cancer and is reported to be associated with poor prognosis, indicating the need for identification of novel agents to improve the efficacy of current therapy or have better activity. Therefore in the present study we explored the anticancer activity of PNU-74654 alone or in combination with gemcitabine in 2 and 3 dimensional cell culture model of pancreatic cancer. Methods: The MTT assay was applied to determine the viability of PC cancerous cells (PCC), while the cytotoxicity of this agent was evaluated in 3D cell culture model (spheroid). The effects of PNU-74654 was investigated in established cell migration/invasion assays. Result: The expression of candidate genes affecting the cell cycle, migration, and Wnt/b-catenin pathway was evaluated at mRNA and/or proteins by RT-PCR or Western blot. PNU-74654 inhibited the cell growth at IC50 of 122±0.4 umol/L, and had a synergistic effect on the antiproliferative properties of gemcitabine by modulating the Wnt pathway. The PNU-74654/gemcitabine combination reduced the migratory and invasiveness of PC cells, compared to control cells through perturbation of E-cadherin. Conclusion: In aggregate our findings demonstrated the profound antitumor properties of PNU-74654 in pancreatic cancer, supporting further studies to evaluate the therapeutic impact of this novel therapy to target Wnt pathway in the treatment of pancreatic cancer.


Biochimie ◽  
2014 ◽  
Vol 106 ◽  
pp. 149-156 ◽  
Author(s):  
Cheng-gui Miao ◽  
Ying-ying Yang ◽  
Xu He ◽  
Cheng Huang ◽  
Yan Huang ◽  
...  

Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 37-49 ◽  
Author(s):  
J.N. Maloof ◽  
J. Whangbo ◽  
J.M. Harris ◽  
G.D. Jongeward ◽  
C. Kenyon

The specification of body pattern along the anteroposterior (A/P) body axis is achieved largely by the actions of conserved clusters of Hox genes. Limiting expression of these genes to localized regional domains and controlling the precise patterns of expression within those domains is critically important for normal patterning. Here we report that egl-20, a C. elegans gene required to activate expression of the Hox gene mab-5 in the migratory neuroblast QL, encodes a member of the Wnt family of secreted glycoproteins. We have found that a second Wnt pathway gene, bar-1, which encodes a beta-catenin/Armadillo-like protein, is also required for activation of mab-5 expression in QL. In addition, we describe the gene pry-1, which is required to limit expression of the Hox genes lin-39, mab-5 and egl-5 to their correct local domains. We find that egl-20, pry-1 and bar-1 all function in a linear genetic pathway with conserved Wnt signaling components, suggesting that a conserved Wnt pathway activates expression of mab-5 in the migratory neuroblast QL. Moreover, we find that members of this Wnt signaling system play a major role in both the general and fine-scale control of Hox gene expression in other cell types along the A/P axis.


Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 581-590 ◽  
Author(s):  
M. Herman

In Caenorhabditis elegans, Wnt signaling pathways are important in controlling cell polarity and cell migrations. In the embryo, a novel Wnt pathway functions through a (beta)-catenin homolog, WRM-1, to downregulate the levels of POP-1/Tcf in the posterior daughter of the EMS blastomere. The level of POP-1 is also lower in the posterior daughters of many anteroposterior asymmetric cell divisions during development. I have found that this is the case for of a pair of postembryonic blast cells in the tail. In wild-type animals, the level of POP-1 is lower in the posterior daughters of the two T cells, TL and TR. Furthermore, in lin-44/Wnt mutants, in which the polarities of the T cell divisions are frequently reversed, the level of POP-1 is frequently lower in the anterior daughters of the T cells. I have used a novel RNA-mediated interference technique to interfere specifically with pop-1 zygotic function and have determined that pop-1 is required for wild-type T cell polarity. Surprisingly, none of the three C. elegans (beta)-catenin homologs appeared to function with POP-1 to control T cell polarity. Wnt signaling by EGL-20/Wnt controls the migration of the descendants of the QL neuroblast by regulating the expression the Hox gene mab-5. Interfering with pop-1 zygotic function caused defects in the migration of the QL descendants that mimicked the defects in egl-20/Wnt mutants and blocked the expression of mab-5. This suggests that POP-1 functions in the canonical Wnt pathway to control QL descendant migration and in novel Wnt pathways to control EMS and T cell polarities.


Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3159-3170 ◽  
Author(s):  
M. Brannon ◽  
J.D. Brown ◽  
R. Bates ◽  
D. Kimelman ◽  
R.T. Moon

XTcf-3 is an HMG box transcription factor that mediates Xenopus dorsal-ventral axis formation. As a Wnt pathway effector, XTcf-3 interacts with beta-catenin and activates the expression of the dorsal organizing gene siamois, while in the absence of beta-catenin, XTcf-3 functions as a transcriptional repressor. We show that XTcf-3 contains amino- and carboxy-terminal repressor domains and have identified a Xenopus member of the C-terminal Binding Protein family of transcriptional co-repressors (XCtBP) as the C-terminal co-repressor. We show that two XCtBP binding sites near the XTcf-3 carboxy-terminus are required for the interaction of XTcf-3 and XCtBP and for the transcriptional repression mediated by the XTcf-3 carboxy-terminal domain. By fusing the GAL4 activation domain to XCtBP we have generated an antimorphic protein, XCtBP/G4A, that activates siamois transcription through an interaction with endogenous XTcf-3. Ectopic expression of XCtBP/G4A demonstrates that XCtBP functions in the regulation of head and notochord development. Our data support a role for XCtBP as a co-repressor throughout Xenopus development and indicate that XCtBP/G4A will be a useful tool in determining how XCtBP functions in various developmental processes.


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