• Molecules and Cells
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• v.39 no.11
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• pp.821-826
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• 2016

The ${\beta}$-catenin functions as an adhesion molecule and a component of the Wnt signaling pathway. In the absence of the Wnt ligand, ${\beta}$-catenin is constantly phosphorylated, which designates it for degradation by the APC complex. This process is one of the key regulatory mechanisms of ${\beta}$-catenin. The level of ${\beta}$-catenin is also controlled by the E3 ubiquitin protein ligase SIAH-1 via a phosphorylation-independent degradation pathway. Similar to ${\beta}$-catenin, STAT3 is responsible for various cellular processes, such as survival, proliferation, and differentiation. However, little is known about how these molecules work together to regulate diverse cellular processes. In this study, we investigated the regulatory relationship between STAT3 and ${\beta}$-catenin in HEK293T cells. To our knowledge, this is the first study to report that ${\beta}$-catenin-TCF-4 transcriptional activity was suppressed by phosphorylated STAT3; furthermore, STAT3 inactivation abolished this effect and elevated activated ${\beta}$-catenin levels. STAT3 also showed a strong interaction with SIAH-1, a regulator of active ${\beta}$-catenin via degradation, which stabilized SIAH-1 and increased its interaction with ${\beta}$-catenin. These results suggest that activated STAT3 regulates active ${\beta}$-catenin protein levels via stabilization of SIAH-1 and the subsequent ubiquitin-dependent proteasomal degradation of ${\beta}$-catenin in HEK293T cells.

• Korean Journal of Plant Resources
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• v.32 no.5
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• pp.442-447
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• 2019

In this study, we evaluated the effect of Rodgersia podophylla leave extracts (RPL) on ${\beta}-catenin$ level in human cancer cells. RPL dose-dependently inhibited cell proliferation in SW480, A549, MDA-MB-231, PC-3 and AsPC-1 cells. RPL dramatically decreased ${\beta}-catenin$ protein level in all cancer cells. However, decreased level of ${\beta}-catenin$ mRNA expression was observed in A549 and AsPC-1 cells. In addition, RPL dramatically attenuated cyclin D1 mRNA expression in all cancer cells. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by RPL in all cancer cells, while RPL-induced downregulation of ${\beta}-catenin$ was inhibited by the inhibition of $GSK-3{\beta}$ by LiCl in MDA-MB-231 cells. RPL phosphorylated ${\beta}-catenin$ and $GSK-3{\beta}$. In addition, the inhibition of $GSK-3{\beta}$ by LiCl attenuated RPL-induced ${\beta}-catenin$ phosphorylation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.92-92
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}$-catenin level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}$-catenin level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}$-catenin protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

• Korean Journal of Plant Resources
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• v.32 no.2
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• pp.153-159
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}-catenin$ level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}-catenin$ level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}-catenin$ protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}-catenin$ protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

• Korean Journal of Pharmacognosy
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• v.52 no.4
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• pp.234-241
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• 2021

Dermal papilla cells (DPCs) are present throughout the hair cycle and play an essential role in hair cycle and hair growth. In this study, we investigated the effect of Carex dispalata on the activation of anagen pathway in DPCs. C. dispalata extract increased the proliferation of DPCs and induced changes in the levels of cell cycle-related proteins. To elucidate the mechanism by which C. dispalata extract stimulates the anagen pathway related to the proliferation of DPCs, we evaluated the effect of C. dispalata extract on the activation of Akt signaling. The increase in the level of phospho-Akt by C. dispalata extract was inhibited by PI3K inhibitor (wortmannin). Wortmannin reduced the effects of C. dispalata extract on the levels of cell cycle-related proteins and proliferation of DPCs. C. dispalata extract increased the levels of Wnt/β-catenin proteins. Wnt/β-catenin inhibitor (XAV939) inhibited changes in cell cycle, cell cycle-related proteins, Wnt/β-catenin proteins, and proliferation induced by C. dispalata extract. C. dispalata extract increased the level of autophagy protein (LC3I/II), and this change was inhibited by XAV939. These results suggest that C. dispalata extract can activate PI3K/Akt, Wnt/β-catenin, and autophagy pathways in DPCs to induce cell proliferation, and thereby promote hair growth phase.

• Journal of Life Science
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• v.21 no.9
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• pp.1301-1309
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• 2011

The major function of adipocytes is to store fat in the form of triglycerides. One of the signaling pathways known to affect adipogenesis, i.e. fat formation, is the WNT/${\beta}$-catenin pathway which inhibits the expression and activity of key regulators of adipogenesis. The purpose of this research is to find genes among the WNT/${\beta}$-catenin pathway which regulate adipogenesis by using small interfering (si) RNA and to find the association of single nucleotide polymorphisms (SNPs) of the gene with serum triglyceride levels in the human population. To elucidate the effects of ${\beta}$-catenin siRNA on adipogenesis key factors, PPAR${\gamma}$ and C/EBP${\alpha}$, we performed real-time PCR and western blotting experiments for the analyses of mRNA and protein levels. It was found that the siRNA-mediated knockdown of ${\beta}$-catenin upregulates adipogenesis key factors. However, upstream regulators of the WNT/${\beta}$-catenin pathway, such as DVL2 and LRP6, had no significant effects compared to ${\beta}$-catenin. These results indicate that ${\beta}$-catenin is a candidate gene for human fat accumulation. In general, serum triglyceride level is a good indicator of fat accumulation in humans. According to statistical analyses of the association between serum triglyceride level and SNPs of ${\beta}$-catenin, -10,288 C>T SNP (rs7630377) in the promoter region was significantly associated with serum triglyceride levels (p<0.05) in 290 Korean subjects. On the other hand, serum cholesterol levels were not significantly associated with SNPs of the ${\beta}$-catenin gene. The results of this study showed that ${\beta}$-catenin is associated with fat accumulation both in vitro and in the human population.

• BMB Reports
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• v.47 no.10
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• pp.540-545
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• 2014

Balanced cell growth is crucial in animal development as well as tissue homeostasis. Concerted cross-regulation of multiple signaling pathways is essential for those purposes, and the dysregulation of signaling may lead to a variety of human diseases such as cancer. The time-honored Wnt/${\beta}$-catenin and recently identified Hippo signaling pathways are evolutionarily conserved in both Drosophila and mammals, and are generally considered as having positive and negative roles in cell proliferation, respectively. While most mainstream regulators of the Wnt/${\beta}$-catenin signaling pathway have been fairly well identified, the regulators of the Hippo pathway need to be more defined. The Hippo pathway controls organ size primarily by regulating cell contact inhibition. Recently, several cross-regulations occurring between the Wnt/${\beta}$-catenin and Hippo signaling pathways were determined through biochemical and genetic approaches. In the present mini-review, we mainly discuss the signal transduction mechanism of the Hippo signaling pathway, along with cross-talk between the regulators of the Wnt/${\beta}$-catenin and Hippo signaling pathways.

• Molecules and Cells
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• v.42 no.1
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• pp.8-16
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• 2019

Mutations in the ${\beta}-catenin$ gene (CTNNB1) have been implicated in the pathogenesis of some cancers. The recent development of cancer genome databases has facilitated comprehensive and focused analyses on the mutation status of cancer-related genes. We have used these databases to analyze the CTNNB1 mutations assembled from different tumor types. High incidences of CTNNB1 mutations were detected in endometrial, liver, and colorectal cancers. This finding agrees with the oncogenic role of aberrantly activated ${\beta}-catenin$ in epithelial cells. Elevated frequencies of missense mutations were found in the exon 3 of CTNNB1, which is responsible for encoding the regulatory amino acids at the N-terminal region of the protein. In the case of metastatic colorectal cancers, in-frame deletions were revealed in the region spanning exon 3. Thus, exon 3 of CTNNB1 can be considered to be a mutation hotspot in these cancers. Since the N-terminal region of the ${\beta}-catenin$ protein forms a flexible structure, many questions arise regarding the structural and functional impacts of hotspot mutations. Clinical identification of hotspot mutations could provide the mechanistic basis for an oncogenic role of mutant ${\beta}-catenin$ proteins in cancer cells. Furthermore, a systematic understanding of tumor-driving hotspot mutations could open new avenues for precision oncology.

• Journal of Life Science
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• v.29 no.8
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• pp.871-878
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• 2019

The aim of this study was to determine the anticancer activities of an 80% methanol extract and various fractions of Rhododendron brachycarpum (RB). The n-hexane fraction of RB showed the highest inhibitory activity (Inhibit concentration $50%=20.2{\pm}1.2{\mu}g/ml$) in HT-29 cells. Colony- and sphereforming abilities were significantly correlated with a decrease in the cell count and size. A TOP/FOP flash reporter assay revealed that the inhibitory activity of the n-hexane fraction of RB ($0.22{\pm}0.02$ fold change) was lower than that of the 80% methanol extract and that of other fractions. The n-hexane and ethyl acetate fractions of RB were predominantly dependent on the expression levels of intracellular ${\beta}-catenin$. Western blotting using $p-GSK3{\beta}$ with only the n-hexane fraction of RB was conducted to examine whether these secondary metabolites reduced ${\beta}-catenin$ degradation. Intracellular ${\beta}-catenin$ regulation resulted in quantitative changes in the nucleus. In summary, these results demonstrate the potential of the n-hexane fraction of RB as a natural anticancer agent.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7277-7284
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• 2015

Background: The Wnt/${\beta}$-catenin signaling pathway is an important regulator of cellular functions such as proliferation, survival and cell adhesion. Wnt/${\beta}$-catenin signaling is associated with tumor initiation and progression; ${\beta}$-catenin mutations explain only 30% of aberrant signaling found in breast cancer, indicating that other components and/or regulation of the Wnt/${\beta}$-catenin pathway may be involved. Objective: We evaluated AXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of ${\beta}$-catenin destruction complex genes in breast cancer patients. Materials and Methods: We collected peripheral blood samples from 102 breast cancer and 102 healthy subjects. The identification of the genetic variation was performed using PCR-RFLPs and DNA sequencing. RT-qPCR was used to determine expression profiles. Results: We found significant association of AXIN2 rs151279728 and rs2240308 polymorphisms with breast cancer risk. Significant increase was observed in AXIN2 level expression in breast cancer patients. Further analyses showed APC, ${\beta}$-catenin, CK1${\alpha}$, GSK3${\beta}$ and PP2A gene expression to be associated to clinic-pathological characteristics. Conclusions: The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of ${\beta}$-catenin destruction complex expression may be found in breast cancer patients, providing additional support for roles of Wnt/${\beta}$-catenin pathway dysfunction in breast cancer tumorigenesis. However, the functional consequences of the genetic alterations remain to be determined.