• Molecules and Cells
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• 제20권2호
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• pp.256-262
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• 2005

The neuronal cytoskeleton is essential for establishment of neuronal polarity, but mechanisms controlling generation of polarity in the cytoskeleton are poorly understood. The nonreceptor tyrosine kinase, Fer, has been shown to bind to microtubules and to interact with several actin-regulatory proteins. Furthermore, Fer binds p120 catenin and has been shown to regulate cadherin function by modulating cadherin-${\beta}$-catenin interaction. Here we show involvement of Fer in neuronal polarization and neurite development. Fer is concentrated in growth cones together with cadherin, ${\beta}$-catenin, and cortactin in stage 2 hippocampal neurons. Inhibition of Fer-p120 catenin interaction with a cell-permeable inhibitory peptide (FerP) increases neurite branching. In addition, the peptide significantly delays conversion of one of several dendrites into an axon in early stage hippocampal neurons. FerP-treated growth cones also exhibit modified localization of the microtubule and actin cytoskeleton. Together, this indicates that the Fer-p120 interaction is required for normal neuronal polarization and neurite development.

• Journal of Korean Neurosurgical Society
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• 제67권6호
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• pp.609-621
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• 2024

Objective : This study analyzed the influence of p120-catenin (catenin [cadherin-associated protein], delta 1 [CTNND1]) on the malignant characteristics of glioma and elucidated the potential underlying mechanism. Methods : The p120 expression level was assessed in the brain tissues of 42 glioma patients and 10 patients with epilepsy by using the immunohistochemical method. Meanwhile, quantitative polymerase chain reaction (QT-PCR) technology was employed to assess the expression of p120 in the brain tissues of 71 glioma patients and 13 epilepsy patients. LN229, U251, and U87 glioma cells were used for in vitro analysis and categorized into four treatment groups : siRNA-blank control (BC) group (no RNA sequence was transfected), siRNA-negative control (NC) group (transfected control RNA sequences with no effect), and siRNA-1 and siRNA-2 groups (two p120-specific interfering RNA transfection). p120 expression in these treatment groups was quantified by western blotting assay. The migratory and invasive capabilities of glioma cells were studied by wound healing assay and Transwell invasion assay, respectively, under different treatment conditions. MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide) assay and cell cycle and apoptosis assay were used to determine glioma cell proliferation and apoptosis, respectively. Enzyme-labeled assay was performed to measure intracellular calcium ion concentration. Immunofluorescence assay was performed for determining microtubule formation and glioma cell distribution. Results : Brain tissues of the glioma group exhibited a remarkable increase in the p120 expression level as compared to brain tissues of the nontumor group (p<0.05). Furthermore, a strong positive correlation was noted between the malignancy degree in glioma brain tissues and p120 expression in Western blotting (r=0.906, p<0.0001) and QT-PCR (F=830.6, p<0.01). Compared to the BC and NC groups, the siRNA transfection groups showed a significant suppression in p120 expression in glioma cells (p<0.05), with a marked attenuation in the invasive, migratory, and proliferative capabilities of glioma cells as well as an increase in apoptotic potential (p<0.05). Enzyme-labeled assay showed a remarkable increase in calcium concentration in glioma cells after siRNA treatment. Immunofluorescence assay revealed that the microtubule formation ability of glioma cells reduced after siRNA treatment. Conclusion : p120 has a pivotal involvement in facilitating glioma cell invasion and proliferation by potentially modulating these processes through its involvement in microtubule formation and regulation of intracellular calcium ion levels.

• Molecules and Cells
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• 제42권3호
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• pp.270-283
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• 2019

This study was aimed to explore if lncRNA MALAT1 would modify chemo-resistance of non-small cell lung cancer (NSCLC) cells by regulating miR-197-3p and p120 catenin (p120-ctn). Within this investigation, we totally recruited 326 lung cancer patients, and purchased 4 NSCLC cell lines of A549, H1299, SPC-A-1 and H460. Moreover, cisplatin, adriamycin, gefitinib and paclitaxel were arranged as chemotherapies, and half maximal inhibitory concentration (IC50) values were calculated to evaluate the chemo-resistance of the cells. Furthermore, mice models of NSCLC were also established to assess the impacts of MALAT1, miR-197-3p and p120-ctn on tumor growth. Our results indicated that MALAT1 and miR-197-3p were both over-expressed within NSCLC tissues and cells, when compared with normal tissues and cells (P < 0.05). The A549, H460, SPC-A-1 and SPC-A-1 displayed maximum resistances to cisplatin ($IC50=15.70{\mu}g/ml$), adriamycin ($IC50=5.58{\mu}g/ml$), gefitinib ($96.82{\mu}mol/L$) and paclitaxel (141.97 nmol/L). Over-expression of MALAT1 and miR-197-3p, or under-expression of p120-ctn were associated with promoted viability and growth of the cancer cells (P < 0.05), and they could significantly strengthen the chemo-resistance of cancer cells (P < 0.05). MALAT1 Wt or p120-ctn Wt co-transfected with miR-197-3p mimic was observed with significantly reduced luciferase activity within NSCLC cells (P < 0.05). Finally, the NSCLC mice models were observed with larger tumor size and weight under circumstances of over-expressed MALAT1 and miR-197-3p, or under-expressed p120-ctn (P < 0.05). In conclusion, MALAT1 could alter chemo-resistance of NSCLC cells by targeting miR-197-3p and regulating p120-ctn expression, which might assist in improvement of chemo-therapies for NSCLC.

• Molecules and Cells
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• 제41권4호
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• pp.320-330
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• 2018

${\delta}$-Catenin, a member of the p120-catenin subfamily of armadillo proteins, reportedly increases during the late stage of prostate cancer. Our previous study demonstrates that ${\delta}$-catenin increases the stability of EGFR in prostate cancer cell lines. However, the molecular mechanism behind ${\delta}$-catenin-mediated enhanced stability of EGFR was not explored. In this study, we hypothesized that ${\delta}$-catenin enhances the protein stability of EGFR by inhibiting its lysosomal degradation that is mediated by c-casitas b-lineage lymphoma (c-Cbl), a RING domain E3 ligase. c-Cbl monoubiquitinates EGFR and thus facilitates its internalization, followed by lysosomal degradation. We observed that ${\delta}$-catenin plays a key role in EGFR stability and downstream signaling. ${\delta}$-Catenin competes with c-Cbl for EGFR binding, which results in a reduction of binding between c-Cbl and EGFR and thus decreases the ubiquitination of EGFR. This in turn increases the expression of membrane bound EGFR and enhances EGFR/Erk1/2 signaling. Our findings add a new perspective on the role of ${\delta}$-catenin in enhancing EGFR/Erk1/2 signaling-mediated prostate cancer.

• KSBB Journal
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• 제24권2호
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• pp.122-130
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• 2009

선별한 신생혈관형성억제제는 EGCG보다도 제어 효과가 나은 천연산물들 중에서 전호, 파고지, 희첨 및 중심으로 그 기전을 밝히고자 하였다. 세포독성은 전호는 0.3 ppm에서 약간의 독성을 나타내었고, 파고지는 10 ppm까지는 독성을 나타내지 않았으며, 희첨 및 산수유는 25 ppm까지 독성을 나타내지 않았다. 세포부착억제작용은 신생혈관의 형성에 중요한 역할을 하기 때문에 cell adhesion 분자인 VCAM-1, ICAM-1 및 E-selectin들에 대하여 ELISA 법으로 살펴보았다. VCAM-1에 대한 천연산물의 작용은 전호 (0.2 ppm, 125%)>파고지 (0.5 ppm, 100%)>희첨 (5.0 ppm, 114%)> 산수유 (5.0 ppm, 111.8%)의 순으로 저해의 강도가 높으며, ICAM-1은 전호 (0.25 ppm, 130%)>파고지 (0.5 ppm, 100%)>희첨 (5.0 ppm, 138%)>산수유 (5.0 ppm, 66.7%)의 순으로 저해되는 것으로 나타났고, 그리고 E-Selectin은 전호 (0.25 ppm, 100%)> 파고지 (1.0 ppm, 128%)>희첨 (5.0 ppm, 120%)>산수유 (5.0 ppm, 100.7%)의 순으로 저해되는 것으로 나타났다. Western blot으로부터, 전호 추출물은 VE-cadherin과 ${\beta}$-catenin의 신호전달을 억제하였으며, 그 하위 신호 전달분자인 Akt도 억제하는 것으로 나타났고, 파고지는 ${\beta}$-catenin의 신호는 억제하지 않는 것으로 보이나, 그 하위그룹의 Akt의 신호전달을 억제하는 것으로 나타났다. 그리고, 희첨은 VE-Cadherin과 하위 그룹의 Akt를 농도의 증가에 따라 확실한 제어를 보이고 있음을 알 수 있었고, 산수유는 하위그룹의 Akt의 신호전달을 억제하는 것으로 나타났다. 4종류의 선택된 천연산물은 세포표면의 신호전달분자 그리고 그 하위 그룹의 Akt를 억제함으로써 NF-kB의 활성을 차단함으로써 신생혈관의 형성을 억제하는 것으로 판단된다. 따라서 4종류의 천연산물 전호, 파고지, 희첨 및 산수유는 전반적으로 낮은 농도에서 세포부착인자의 발현을 억제하였고, 신호전달 분자들을 억제함으로써 신생혈관 형성 억제에 따른 항비만제제로서 충분한 가능성을 보였다.