• Microbiology and Biotechnology Letters
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• v.42 no.1
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• pp.89-92
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• 2014

The Wnt/${\beta}$-catenin pathway plays important roles in a variety of biological processes, such as cell proliferation, differentiation, and organ development. Here, we used a cell-based reporter assay to identify bryostatin-1, a natural macrocyclic lactone, as an inhibitor of the Wnt/${\beta}$-catenin pathway. Bryostatin-1 suppressed ${\beta}$-catenin response transcription (CRT), which was activated by a Wnt3a-conditioned medium (Wnt3a-CM), through a decrease in the intracellular ${\beta}$-catenin protein levels, without affecting its mRNA level. In addition, pharmacological inhibition of proteasome abrogated bryostatin-1-mediated down-regulation of the ${\beta}$-catenin protein level. Our findings suggest that bryostatin-1 attenuates the Wnt/${\beta}$-catenin pathway through the promotion of proteasomal degradation of ${\beta}$-catenin.

• The Zoological Society Korea : Newsletter
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• v.18 no.1
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• pp.16-25
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• 2001

Wnt signaling의 주요 분자인 $\beta$-catenin의 기능과 조절에 관한 연구, 특히 TCF family 단백질과 함께 작용하는 신호전달에 관한 연구가 최근에 활발히 진행되고 있다. $\beta$-catenin 단백질은 Drosophila나 Xenopus의 발생초기에 중요한 역할을 한다는 것이 알려져 있고 Wnt (Wingless) 단백질에 의하여 활성화되는 신호전달 과정에 관여한다고 알려져 있으므로, TCF 단백질들이 Wnt signalling pathway에 작용한다는 것을 의미한다. 즉, $\beta$-catenin/TCF complex는 발생초기의 세포의 운명을 결정하는 세포의 분화에 중요하리라 생각된다. 또한 $\beta$-catenin/TCF complex는 세포의 암화에도 중요하다는 것이 보고되었다. 정상세포의 경우, $\beta$-catenin은 APC 라는 tumor suppressor에 의하여 결합하고 단백질의 분해가 유도되어 핵 안의 TCF와 결합하지 못하는데, 암세포의 경우 APC가 결실되었거나 $\beta$-catenin의 양이 과도하게 발현되어 암세포화 되는 것으로 보인다. 즉, $\beta$-catenin은 일종의 oncogene으로 작용하는 단백질이며, 그 작용에 필수적인 전사인자가 TCF라는 것이다. 특히, 대장암세포에서 이 $\beta$-catenin/TCF complex에 의해 활성화되는 유전자로서 c-myc과 cyclin Dl 등이 있는 것으로 보아, $\beta$-catenin/TCF 단백질은 세포의 증식 및 사멸에 관여하는 단백질들의 발현을 조절하는 매우 중요한 인자라고 생각된다.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.4
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• pp.305-310
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• 2006

Abnormal activation of the Wnt/${\beta}$-catenin pathway and subsequent up-regulation of ${\beta}$-catenin response transcription (CRT) are associated with the development of colon cancer. Thus, the Wnt/${\beta}$-catenin pathway is an attractive target for chemoprevention and treatment of this cancer. In this study, we used a cell-based screen to identify a methanol extract of Dictyota dichotoma (EDD) that suppresses the Wnt/${\beta}$-catenin pathway without altering the level of ${\beta}$-catenin protein and reduces the expression of cyclin D1, which is a known ${\beta}$-catenin/T cell factor (TCF)-dependent gene. EDD inhibited the growth of various colon cancer cells. Our findings suggest that EDD can potentially be used as a chemopreventive agent against colon cancer.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.161-169
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• 2018

We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of ${\beta}-catenin$ in C2C12 cells. However, the relationship between EGF-induced SMURF1 and ${\beta}-catenin$ expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate ${\beta}-catenin$ expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of ${\beta}-catenin$ mRNA and protein. Overexpression of SMURF1 downregulated ${\beta}-catenin$ mRNA and protein, whereas knockdown of SMURF1 increased ${\beta}-catenin$ expression and blocked EGF-induced ${\beta}-catenin$ downregulation. Knockdown of ${\beta}-catenin$ enhanced cell migration and invasion of MDAMB231 cells, while ${\beta}-catenin$ overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of ${\beta}-catenin$ enhanced vimentin expression and decreased cytokeratin expression, whereas ${\beta}-catenin$ overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates ${\beta}-catenin$ in a SMURF1-dependent manner and that ${\beta}-catenin$ downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.

• Microbiology and Biotechnology Letters
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• v.40 no.1
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• pp.50-56
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• 2012

The Wnt/${\beta}$-catenin signaling pathway regulates diverse developmental processes and adult tissue homeostasis. Inappropriate regulation of this pathway has been associated with human diseases, such as cancers, osteoporosis, and Alzheimer's disease. Using a cell-based chemical screening with natural compounds, we discovered silybin, a plant flavonoid isolated from the Silybum marianum, which activated the Wnt/${\beta}$-catenin signaling pathway in a synergy with Wnt3a-conditioned medium (Wnt3a-CM). In the presence of Wnt3a-CM, silybin up-regulated ${\beta}$-catenin response transcription (CRT) in HEK293-FL reporter cells and 3T3-L1 preadipocytes through stabilization of intracellular ${\beta}$-catenin protein. Silybin and Wnt3a-CM synergistically reduced expression of important adipocyte marker genes including peroxisome-proliferator-activated $receptor{\gamma}$ ($PPAR{\gamma}$) and CAATT enhancer-binding protein ${\alpha}$ (C/$EBP{\alpha}$) in 3T3-L1 preadipocytes, accompanied by the activation of Wnt/${\beta}$-catenin signaling pathway. Taken together, our findings indicate that silybin is a small-molecule synergist of the Wnt/${\beta}$-catenin signaling pathway and can be used as a controllable reagent for investigating biological processes that involve the Wnt/${\beta}$-catenin signaling pathway.

• 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.

• Journal of Life Science
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• v.23 no.7
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• pp.947-954
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• 2013

The Wnt/${\beta}$-catenin signaling pathway is an evolutionarily conserved signaling network that is critical for embryonic development and adult tissue maintenance. In addition, aberrant activation of Wnt/${\beta}$-catenin signaling is implicated in the formation of various human diseases, including cancers. Thus, study of the underlying molecular mechanism of Wnt/${\beta}$-catenin signaling regulation is important to understand and treat diseases. Inhibition of aberrant Wnt pathway activity in cancer cell lines efficiently blocks their growth, highlighting the great potential of therapeutics designed to achieve this in cancer patients. Recently, protein kinases have emerged as key regulating components of Wnt/${\beta}$-catenin signaling. In this review, we provide the most recent information on Wnt/${\beta}$-catenin signaling, describe protein kinases involved in Wnt/${\beta}$-catenin signaling, and discuss their potential as drug targets.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.93-93
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• 2019

In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of branches from Taxillus yadoriki parasitic to Neolitsea sericea (TN-NS-B) against human lung cancer cells, A549. TY-NS-B dose-dependently suppressed the growth of A549 cells. TY-NS-B decreased ${\beta}$-catenin protein level, but not mRNA level in A549 cells. The downregulation of ${\beta}$-catenin protein level by TY-NS-B was attenuated in the presence of MG132. Although TY-NS-B phosphorylated ${\beta}$-catenin protein, the inhibition of $GSK3{\beta}$ by LiCl did not blocked the reduction of ${\beta}$-catenin by TY-NS-B. In addition, TY-NS-B decreased ${\beta}$-catenin protein in A549 cells transfected with Flag-tagged wild type ${\beta}$-catenin or Flag-tagged S33/S37/T41 mutant ${\beta}$-catenin construct. Our results suggested that TN-NS-B may downregulate ${\beta}$-catenin protein level independent on GSK3${\beta}$-induced ${\beta}$-catenin phosphorylation. Based on these findings, TY-NS-B may be a potential candidate for the development of chemopreventive or therapeutic agents for human lung cancer.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.356-361
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• 2007

To investigate the region of ErbB2 for the $ErbB2-{\beta}-catenin$ interaction, a proteasome $resistant-{\beta}-catenin$ and various ErbB2 constructs were transfected in COS7 cells. ErbB2 proteins were immunoprecipitated, and coimmunoprecipitated ${\beta}-catenin$ was examined by Western blotting. ${\beta}-catenin$ coimmunoprecipitated with full length ErbB2. Of the truncated ErbB2 proteins DT (1-1123), DHC (1-1031) and DK (1-750), the ErbB2 constructs containing the kinase domain, DT and DHC, precipitated together with ${\beta}-catenin$ but DK containing no kinase domain did not. To further test the requirement of the kinase domain for ${\beta}-catenin-ErbB2$ interaction, the presence of ${\beta}-catenin$ in the immunocomplex was examined following transfection with an ErbB2 mutant (${\triangle}750-971$) whose kinase domain is internally deleted and subsequent immunoprecipitation of the ErbB2 mutant. ${\beta}-catenin$ was not detected in the immunocomplex. These results suggest that the ErbB2 kinase domain comprises a potential site for ${\beta}-catenin$ binding to the receptor tyrosine kinase.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.68-68
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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.