• Title/Summary/Keyword: CYR61

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Role of the CCN protein family in cancer

  • Kim, Hyungjoo;Son, Seogho;Shin, Incheol
    • BMB Reports
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    • v.51 no.10
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    • pp.486-492
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    • 2018
  • The CCN protein family is composed of six matricellular proteins, which serve regulatory roles rather than structural roles in the extracellular matrix. First identified as secreted proteins which are induced by oncogenes, the acronym CCN came from the names of the first three members: CYR61, CTGF, and NOV. All six members of the CCN family consist of four cysteine-rich modular domains. CCN proteins are known to regulate cell adhesion, proliferation, differentiation, and apoptosis. In addition, CCN proteins are associated with cardiovascular and skeletal development, injury repair, inflammation, and cancer. They function either through binding to integrin receptors or by regulating the expression and activity of growth factors and cytokines. Given their diverse roles related to the pathology of certain diseases such as fibrosis, arthritis, atherosclerosis, diabetic nephropathy, retinopathy, and cancer, there are many emerging studies targeting CCN protein signaling pathways in attempts to elucidate their potentials as therapeutic targets.

Microarray and Quantitative PCR Analysis of Gene Expression Profiles in Response to Treatment with Tomato Leaf Extract in MCF-7 Breast Cancer Cells

  • Amid, Azura;Chik, Wan Dalila Wan;Jamal, Parveen;Hashim, Yumi Zuhanis Has-Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6319-6325
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    • 2012
  • We previously found cytotoxic effects of tomato leaf extract (TLE) on the MCF-7 breast cancer cell line. The aim of this study was to ascertain the molecular mechanisms associated with the usage of TLE as an anticancer agent by microarray analysis using mRNA from MCF-7 breast cancer cells after treatment with TLE for 1 hr and 48 hrs. Approximately 991 genes out of the 30,000 genes in the human genome were significantly (p<0.05) changed after the treatment. Within this gene set, 88 were significantly changed between the TLE treated cells and the untreated MCF-7 cells (control cells) with a cut-off fold change >2.00. In order to focus on genes that were involved in cancer cell growth, only twenty-nine genes were selected, either down-regulated or up-regulated after treatment with TLE. Microarray assay results were confirmed by analyzing 10 of the most up and down regulated genes related to cancer cells progression using real-time PCR. Treatment with TLE induced significant up-regulation in the expression of the CRYAB, PIM1, BTG1, CYR61, HIF1-${\alpha}$ and CEBP-${\beta}$ genes after 1 hr and 48 hrs, whereas the TXNIP and THBS1 genes were up-regulated after 1 hr of treatment but down-regulated after 48 hrs. In addition both the HMG1L1 and HIST2H3D genes were down-regulated after 1 hr and 48 hrs of treatment. These results demonstrate the potent activity of TLE as an anticancer agent.

A Study for the Mechanism of Abnormal Proliferation in Vascular Endothelial Cells using Inhibitors to the Signal Transduction Pathway (신호전달 경로의 저해제를 이용한 혈관 내피세포의 비정상적인 증식 기전에 대한 연구)

  • Bae, Yong Chan;Park, Suk Young;Nam, Su Bong;Herh, Jae Young;Kang, Young Seok
    • Archives of Plastic Surgery
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    • v.33 no.1
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    • pp.5-12
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    • 2006
  • Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, take a significant role in signal transduction pathway of angiogenesis. The authors utilized the inhibitors, targeting the formation of three co-enzyme in signal transduction pathway in order to quantify the suppression of abnormal vascular endothelial cell proliferation induced by DMH, to compare the level suppression in each up-regulated growth factors, CTGF, CYR61, $ITG{\beta}1$, FHL2, and to identify the relationship between abnormal cell proliferation and signal transduction pathway. Five groups were established; Control group, Group of DMH, Group of DMH-mixed Herbimycin, inhibitor of protein tyrosine kinase, Group of DMH-mixed Calphostin C, inhibitor of protein kinase C, Group Of Dmh-Mixed 10U Catalase, Inhibitor Of oxidase. The rise of vascular endothelial cell was compared by MTT assay, and four growth factors were analysed with RT-PCR method, at pre-administration, 4, 8, 12, and 24 hours after administration. In comparison of abnormal proliferation of vascular endothelial cell induced by DMH, suppression was noticed in Herbimycin and Calphostin C group, and Calphostin C group revealed higher suppression effect. Nevertheless, Catalase group did not have any suppression. In manifestation of four growth factors, Herbimycin and Calphostin C group presented similar manifestation with control group, except in $ITG{\beta}$. Catalse group had similar manifestation with DMH group in all four growth factors. Abnormal proliferation of vascular endothelial cell induced by DMH have a direct relationship with PTK and PKC, more specifically to PKC. Oxidase was confirmed not to have any relevance.

Root Bark of Morus Alba Suppresses the YAP Activity through Activation of Classical Hippo Signaling Pathway (상근피의 Hippo 신호전달 경로 활성화를 통한 YAP 억제 효능)

  • Cho, You Na;Choi, Da Bin;Jeong, Han Sol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.4
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    • pp.191-197
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    • 2019
  • This study aims to evaluate the effects of the root bark of Morus alba (RMA) on the regulation of the Hippo-YAP pathway. Hippo-YAP signaling is a critical regulator in controlling organ size and tissue homeostasis. Hippo, the serine/threonine kinase phosphorylate the LATS. Phosphorylated LATS then phosphorylates and inactivates the YAP and TAZ, which are two closely related transcriptional co-activator. Here we report RMA activates the Hippo signaling, thereby inhibits the YAP/TAZ activity. First, we examine the cytotoxic effects of RMA by MTT assay. RMA was cytotoxic at concentrations higher than $50{\mu}g/ml$ in HEK293A cells. The reporter gene assay was performed to measure the activity of TEAD, a key transcription factor that controls cell growth and proliferation. RMA significantly suppressed the luciferase activity. By phos-taq gel shift assay, and western blotting, we showed that RMA enhanced the phosphorylation of YAP in wild type cells, but not in LATS1/2 knock out cells, which means RMA activates classical Hippo pathway. RMA induced the cytoplasmic sequestration of YAP. RMA also suppressed the mRNA expression of CTGF and CYR61; the two major YAP dependent genes. Taken together, RMA is considered to be a good candidate for proliferative disease such as cancer, by facilitating cell death through activating the Hippo signaling pathway.

Anti-tumorigenic Effects of Angelica gigase Nakai Extract on MBA-MB-231 through Regulating Lats1/2 Activation (유방암세포에서 LATS1/2 활성에 의한 당귀 추출물의 항암효과)

  • Kim, Cho-Long;Kim, Nambin;Jeong, Han-Sol;Shin, Yu-Su;Mo, Jung-Soon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.4
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    • pp.177-183
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    • 2020
  • The Hippo-YAP signaling pathway is critical for cell proliferation, survival, and self-renewal in both Drosophila and mammals. Disorder of Hippo-YAP pathway leads to tumor development, progression and poor prognosis in various cancers. YAP/TAZ are the key downstream effectors of the Hippo pathway and they can be inhibited through LATS1/2, core kinases in the Hippo pathway, mediated phosphorylation. In this study, we investigated the effect of Angelica gigas Nakai extract (AGNE) on Hippo-YAP/TAZ pathway. First, ANGE induced YAP/TAZ phosphorylation and dissociation of the YAP/TAZ-TEAD transcription complex. By qRT-PCR, we found that ANGE inhibits the expression of YAP/TAZ-TEAD target gene, CTGF and CYR61. In addition, the transcriptional activity of YAP/TAZ was not suppressed significantly in LATS1/2 double-knockout (DKO) cells by ANGE compared to LATS1/2 wild-type (WT) cells, which means AGNE inhibits YAP/TAZ signaling through direct action on LATS1/2. Further, it was confirmed that AGNE-induced activation of LATS1/2 inhibited the migration potential of the vector-expressing cells by suppressing YAP/TAZ activity. The reduced migration potential was restored in active YAP-TEAD expressing cells. Taken together, the results of this study indicate that ANGE downregulates YAP/TAZ signaling in cells through the activation of LATS1/2.

Effect of Resistance Training on Skeletal Muscle Gene Expression in Rats: a Beadarray Analysis (저항성 운동이 골격근 유전자 발현에 미치는 영향: Beadarray 분석)

  • Oh, Seung-Lyul;Oh, Sang-Duk
    • Journal of Life Science
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    • v.23 no.1
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    • pp.116-124
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    • 2013
  • The aim was to examine resistance exercise-related genes after 8 weeks of resistance training. Thirty-two male Sprague-Dawley rats were divided into four groups: 4 weeks sedentary (4 wks CON, n=8), 8 weeks sedentary (8 wks CON, n=8), 4 weeks exercise training (4 wks REG, n=8), and 8 weeks exercise training (8 wks REG, n=8). The rats were trained to climb a 1-m vertical incline (85-degree), with weights secured to their tails. They climbed 10 times, 3 days per week, for 8 consecutive weeks. Skeletal muscle was taken from the flexor halucis longus after the exercise training. After separating the total RNA, large-scale gene expression was investigated by beadarray (Illumina RatRef-12 Expression BeadChip) analysis, and qPCR was used to inspect the beadarray data and to analyze the RNA quantitatively. The detection p-value for the genes was p<0.01, the M-value {M=$log_2$(condition)-$log_2$(reference)} was >1.0, and the DiffScore was >20. In total, the expression of 30 genes significantly increased 4 weeks after the exercise training, and the expression of six genes decreased. At 8 weeks, the expression of five genes significantly increased and that of 12 decreased. Several genes are potentially involved in resistance exercise and muscle hypertrophy, including 1) regulation of cell growth (IGFBP1, PLA2G2A, OKL38); 2) myogenesis (CSRP3); 3) tissue regeneration and muscle development (MUSTN1, MYBPH); 4) hypertrophy (CYR61, ATF3, NR4A3); and 5) glucose metabolism (G6PC, PCK1). These results may help to explain previously reported physiological changes of the skeletal muscle and suggest new avenues for further investigation.

GENE EXPRESSION PATTERNS INDUCED BY $TAXOL^{(R)}$ AND CYCLOSPORIN A IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE USING CDNA MICROARRAY (cDNA Microarray를 이용한 구강편평세포암종 세포주에서 $Taxol^{(R)}$과 Cyclosporin A로 유도된 유전자 발현양상)

  • Kim, Yong-Kwan;Lee, Jae-Hoon;Kim, Chul-Hwan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.3
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    • pp.202-212
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    • 2006
  • It is well-known that paclitaxel($Taxol^{(R)}$), which is extracted from the pacific and English yew, has been used as a chemotherapeutic agent for ovarian carcinoma and advanced breast carcinoma and Cyclosporin A, which is highly lipophilic cyclic peptide and isolated from a fungus, has been also used as an useful immunosuppressive drug after transplantation and is associated with cellular apoptosis. Since 1953, in which James Watson, Rosalind Franklin and Francis Crick discovered the double helical structure of DNA, a few kinds of techniques for identifying gene expression have been developed. In postgenomic period, many of researchers have used the DNA microarray which is high throughput screening technique to screen large numbers of gene expression simultaneously. In this study, we searched and screened the gene expression in the oral squamous cell carcinoma cell lines treated with $Taxol^{(R)}$, cyclosporin or cyclosporin combined with $Taxol^{(R)}$ using cDNA microarray. The results were as following; 1. It was useful that the appropriate concentration of Cyclosporin A and $Taxol^{(R)}$ used in oral squamous cell carcinoma cell line was under 1${\mu}g/ml$ and 3${\mu}g/ml$. 2. In the experimental group in which $Taxol^{(R)}$ and $Taxol^{(R)}$ + Cyclosporin A were used, the cell growth was extremely decreased. 3. In the group in which Cyclosporin A was used, the MTT assay was rarely decreased which means the activity of succinyl dehydrogenase is remained in mitochondria but in the group in which the mixture of Cyclosporin A and $Taxol^{(R)}$ were used, the MTT assay was extremely decreased. 4. In the each group in which Cyclosporin A(3 ${\mu}g/ml$) and $Taxol^{(R)}$(1 ${\mu}g/ml$) were used, the cell arrest was appeared in $G_2/M$ phase and in the group in which $Taxol^{(R)}$(3 ${\mu}g/ml$) was used, the cell arrest was appeared in both S phase and $G_2/M$ phase. 5. In the oral squamous cell carcinoma cell line treated with $Taxol^{(R)}$, several genes including ANGPTL4, RALBP1 and TXNRD1, associated with apoptosis, SUI1, MAC30, RRAGA and CTGF, related with cell growth, HUS1 and DUSP5, related with cell cycle and proliferation, ATF4 and CEBPG, associated with transcription factor, BTG1 and VEGF, associated with angiogenesis, FDPS, FCER1G, GPA33 and EPHA4 associated with signal transduction and receptor activity and AKR1C2 and UGTA10 related with carcinogenesis were detected in increased levels. The genes that showed increaced expression in the oral squamous cell carcinoma cell line treated with Cyclosporin A were CYR61, SERPINB2, SSR3 and UPA3A which are known as genes associated with cell growth, carcinogenesis, receptor activity and transcription factor. The genes expressed in the HN22 cell line treated with cyclosporin combined with $taxol^{(R)}$ were ALCAM and GTSE1 associated with cancer invasiveness and cell cycle regulation.