• Title/Summary/Keyword: metastasis suppressor

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Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

  • Prabhu, V. Vinod;Siddikuzzaman, Siddikuzzaman;Grace, V.M. Berlin;Guruvayoorappan, C.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3539-3548
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    • 2012
  • The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

New Tumor Metastasis Suppressor Gene from Korean Tiger Shark (Scyliorhinus torazame)

  • CHO Jung Jong;LEE Jae Hyung;LEE Sang-Jun;LIM Woon Ki;KIM Yung-Jin;KIM Kyu-Won;KIM Young Tae
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.30 no.6
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    • pp.984-991
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    • 1997
  • New tumor suppressor gene, snm23, homologous to human nm23/NDP kinase (human nucleoside diphosphate kinase) gene whose product has a tumor metastasis inhibitory activity, was first cloned from Korean tiger shark (Scyliorhinus forazame) skin cDNA library constructed by using a $\lambda$ ZAP-II cDNA synthesis kit. About $1\times10^5$ plaques were screened and several positive plaques were isolated and confirmed by second screening. The phagemid containing a positive clone from the Uni-Zap XR vector was excised in vivo and the gene containing the tumor metastasis suppressor protein was named as snm23. Cloned gene, snm23, was sequenced with ABI-PRISM 310 Genetic Analyzer. The nucleotide and deduced amino acid sequences of snm23 have shown an open reading frame consisting of 450 base pairs that correspond to a protein of 150 amino acid residues, with a calculated molecular mass of 16.8 kDa. Sequence comparison of snm23 with human nm23/NDP kinase was performed by using Blast protein data base of National Center for Biotechnology Information. In order to determine tissue specificity, reverse transcription-polymerase chain reaction (RT-PCR) was used. Good expression level of snm23/NDP kinase was detected at the tissues from skin, cartilage, and liver of Korean tiger shark.

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Alteration of Multiple Tumor Suppressor Genes in Head and Neck Squamous Cell Carcinoma (두경부 편평상피세포암에서 종양억제유전자들의 변이)

  • Song Si-Youn;Park Kang-Shik;Bai Chang-Hoon
    • Korean Journal of Head & Neck Oncology
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    • v.20 no.2
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    • pp.147-155
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    • 2004
  • Objectives: Head and neck squamous cell carcinoma (HNSCC) is the most common head and neck malignant tumor. The molecular genetic changes involving both oncogenes and tumor suppressor genes are known to be involved in head and neck squamous cell carcinogenesis, but the roles of the known tumor suppressor genes in carcinogenesis are not fully elucidated. The objectives of this study are to demonstrate the genetic alterations including the loss of heterozygosity (LOH) , amplification, and microsatellite instability of known tumor suppressor genes in HNSCC and to evaluate the relationship between genetic alterations of tumor suppressor genes and clinicopathologic features. Materials and Methods: Genetic alterations of 10 micro satellite markers of the 6 known tumor suppressor genes (APC, EXT1, DPC4, p16, FHIT, and PTEN) were analysed by DNA-PCR in paraffin-embedded histologically confirmed HNSCC specimens. Results: The genetic alterations of tumor suppressor genes were found frequently. Among the genetic alterations, LOH was most frequently found one. LOH was found frequently in APC (45.4%), EXT1 (36.4%), DPC4 (54.5%), and p16 (50%), but not found in FHIT. Also, the author found that abnormalities of APC gene was related to cervical lymph node metastasis and recurrence and that abnormalities of EXT1 gene were coexisted with those of APC gene or DPC4 gene. But these coexistences had no correlation with clinical features. Conclusion: These results suggested that APC, EXT1, p16, and DPC4 genes might play important roles and multiple tumor suppressor genes may participate dependently or independently in the carcinogenesis of HNSCC. These results also suggested that APC gene might relate to prognosis.

microRNA-29b: an Emerging Player in Human Cancer

  • Liu, Hao;Wang, Bin;Lin, Jie;Zhao, Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9059-9064
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    • 2014
  • MicroRNAs (miRNAs) are ubiquitously expressed small, non-coding RNAs that negatively regulate gene expression at a post transcriptional/translational level. They have emerging as playing crucial roles in cancer at all stages ranging from initiation to metastasis. As a tumor suppressor miRNA, aberrant expression of microRNA-29b (miR-29b) has been detected in various types of cancer, and its disturbance is related with tumor development and progression. In this review, we summarize the latest findings with regard to the tumor suppressor signatureof miR-29b and its regulatory mechanisms. Our review highlights the diverse relationships between miR-29b and its target genes in malignant tumors.

Beyond the Molecular Facilitator, CD82: Roles in Metastasis Suppressor, Stem Cell Niche, Muscle Regeneration, and Angiogenesis (분자 촉진제를 넘어, CD82: 전이억제자, 줄기세포 니쉬, 근육 재생 및 혈관신생에서의 역할)

  • Lee, Hyun-Chae;Han, Jung-Hwa;Hur, Jin
    • Journal of Life Science
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    • v.31 no.9
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    • pp.856-861
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    • 2021
  • CD82/KAI1, identified as a metastasis suppressor, was initially known only as a molecular facilitator, but its various functions have recently been revealed. CD82 plays an important role in the stem-progenitor cell, angiogenesis, and muscle. We would like to introduce the recently reported functions and roles of CD82 in this review. CD82 is a member of the tetraspanin family, which consists of four transmembrane domains. The interaction between CD82 and cell adhesion molecules suppresses the metastasis of cancer. CD82 regulates the cell cycle of stem-progenitor cells in the stem cell niche. In the bone marrow, CD82 is expressed on long-term repopulating hematopoietic stem cells (LT-HSCs), which show multipotent differentiation potential. The interaction between CD82 and Duffy antigen receptor for chemokines (DARC) induces quiescence in LT-HSCs. CD82 also regulates Rac1 activity, resulting in the homing and engraftment of HSCs into the bone marrow niche. Besides, CD82 maintains the differentiation potential of muscle stem cells and prevents angiogenesis by inhibiting the expression of cytokines, such as IL-6 and VEGF and adhesion molecules in endothelial cells. CD82 is a key membrane protein that distinguishes the hierarchy of stem-progenitor cells, and is also important for amplification and verification of cellular resources. Further studies on the function of CD82 in various organs and cells are expected to advance cell biology and cell therapy.

Clinicopathological Significance of Large Tumor Suppressor (LATS) Expression in Gastric Cancer

  • Son, Myoung Won;Song, Geum Jong;Jang, Si-Hyong;Hong, Soon Auck;Oh, Mee-Hye;Lee, Ji-Hye;Baek, Moo Jun;Lee, Moon Soo
    • Journal of Gastric Cancer
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    • v.17 no.4
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    • pp.363-373
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    • 2017
  • Purpose: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). Materials and Methods: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. Results: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (${\geq}65$, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. Conclusions: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.

Anti-metastatic mechanism of mountain cultivated wild ginseng in human cancer cell line

  • Jang, S.B.;Lim, C.S.;Jang, J.H.;Kwon, K.R.
    • Journal of Pharmacopuncture
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    • v.13 no.1
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    • pp.37-43
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    • 2010
  • Objective : Ginseng is one of most widely used herbal medicine. Ginseng showed anti-metastasis activities. However, its molecular mechanisms of action are unknown. So we want to report the wild ginseng repress which plays key roles in neoplastic epithelial-mesenchymal transition process. Methods : Treatment of the human colorectal carcinoma LOVO cells and human gastric carcinoma SNU601 cells with the increased concentrations of cultivated wild ginseng extracts resulted in a gradual decrease in the AXIN2 gene expression. Results : Metastasis-suppressor genes, maspin and nm23 was not affected by the treatment of ginseng extracts in LOVO cells. Moreover, the mountain cultivated wild ginseng or mountain wild ginseng are similar in their inhibitory effects on the expression of AXIN2 gene, but are substantially stronger than cultivated ginseng. Conclusion : We described the novel mechanism of wild ginseng-induced anti-metastasis activity by repressing the expression of AXIN2 gene that plays key roles in epithelial-mesenchymal transition process.

Hypermethylation of TET1 Promoter Is a New Diagnosic Marker for Breast Cancer Metastasis

  • Sang, Yi;Cheng, Chun;Tang, Xiao-Feng;Zhang, Mei-Fang;Lv, Xiao-Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1197-1200
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    • 2015
  • Breast cancer metastasis is a major cause of cancer-related death in women. However, markers for diagnosis of breast cancer metastasis are rare. Here, we reported that TET1, a tumor suppressor gene, was downregulated and hypermethylated in highly metastatic breast cancer cell lines. Moreover, silencing of TET1 in breast cancer cells increased the migration and spreading of breast cancer cells. In breast cancer clinical samples, TET1 expression was reduced in LN metastases compared with primary tissues. Besides, the methylation level of the TET1 promoter was increased significantly in LN metastases. Taken together, these findings indicate that promoter hypermethylation may contribute to the downregulation of TET1 and could be used as a promising marker for diagnosis in patients with breast cancer metastasis.