scholarly journals Dickkopf-Related Protein 2 is Epigenetically Inactivated and Suppresses Colorectal Cancer Growth and Tumor Metastasis by Antagonizing Wnt/β-Catenin Signaling

2017 ◽  
Vol 41 (5) ◽  
pp. 1709-1724 ◽  
Author(s):  
Can Wang ◽  
Yujuan Yue ◽  
Bianfei Shao ◽  
Zhu Qiu ◽  
Junhao Mu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Ectopic Expression ◽  
Colon Tumor ◽  
Tumor Cell Lines ◽  
Related Protein ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Colon Tumor Cell ◽  
Dkk2 Expression

Background/Aims: Aberrant activation of the Wnt/β-catenin signaling pathway plays a key role in the pathogenesis of multiple tumors including digestive cancers. Recent studies have reported that Dickkopf-related protein 2 (DKK2) is epigenetically inactivated in numerous types of cancers and that its gene products exhibit tumor-suppressive properties. However, the biological functions and underlying molecular mechanisms of DKK2 in colon carcinoma remains obscure. Methods: We examined the expression of DKK2 in colon tumor cell lines by RT-PCR and its promoter methylation status in colon tumor cell lines and primary tumors by methylation-specific PCR (MSP). Ectopic expression of DKK2 was measured by RT-PCR prior to the other experiments. To investigate the function of DKK2, we assayed colony formation and cell proliferation, utilized flow cytometric analyses of the cell cycle and acridine orange/ethidium bromide (AO/EB) fluorescence staining for apoptosis, and examined wound healing, transwell migration and tumor growth in vivo. Western blots were used to explore the mechanisms of DKK2 in epithelial- mesenchymal transition and canonical Wnt/β-catenin signaling. Results: We show here that downregulation or silencing of DKK2 was closely associated with the hypermethylation status of its promoter and that DKK2 expression could be restored by demethylation treatment. Methylation of the DKK2 promoter was detected in nearly all tumors and tumor-adjacent tissues, but not in normal colon tissues. Ectopic expression of DKK2 in colon cell lines HCT116 and HT-29 inhibited colony formation and cell viability by inducing cell cycle G0/G1 arrest and apoptosis, and growth of stable DKK2-infected HCT116 cells in nude mice was decreased compared to controls. Furthermore, DKK2 restrained cell migration through partial reversal of epithelial-to- mesenchymal transition and also by downregulating several stem cell markers. Our data further showed that restoration of DKK2 expression resulted in downregulation of active β-catenin and its downstream target genes. Conclusion: DKK2 appears to be a functional tumor suppressor regulating tumorigenesis of colorectal cancer by antagonizing Wnt/β-catenin signaling.

scholarly journals miR551b Regulates Colorectal Cancer Progression by Targeting the ZEB1 Signaling Axis

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 735 ◽  
Author(s):  
Kwang Seock Kim ◽  
Dongjun Jeong ◽  
Ita Novita Sari ◽  
Yoseph Toni Wijaya ◽  
Nayoung Jun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Xenograft Model ◽  
Mesenchymal Transition ◽  
Normal Tissues

Our current understanding of the role of microRNA 551b (miR551b) in the progression of colorectal cancer (CRC) remains limited. Here, studies using both ectopic expression of miR551b and miR551b mimics revealed that miR551b exerts a tumor suppressive effect in CRC cells. Specifically, miR551b was significantly downregulated in both patient-derived CRC tissues and CRC cell lines compared to normal tissues and non-cancer cell lines. Also, miR551b significantly inhibited the motility of CRC cells in vitro, including migration, invasion, and wound healing rates, but did not affect cell proliferation. Mechanistically, miR551b targets and inhibits the expression of ZEB1 (Zinc finger E-box-binding homeobox 1), resulting in the dysregulation of EMT (epithelial-mesenchymal transition) signatures. More importantly, miR551b overexpression was found to reduce the tumor size in a xenograft model of CRC cells in vivo. Furthermore, bioinformatic analyses showed that miR551b expression levels were markedly downregulated in the advanced-stage CRC tissues compared to normal tissues, and ZEB1 was associated with the disease progression in CRC patients. Our findings indicated that miR551b could serve as a potential diagnostic biomarker and could be utilized to improve the therapeutic outcomes of CRC patients.

Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines

1992 ◽  
Vol 62 (2) ◽  
pp. 95-105 ◽  
Author(s):  
C.W. Taylor ◽  
Y.S. Kim ◽  
K.E. Childress-Fields ◽  
L.C. Yeoman
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Colon ◽  
Colon Tumor ◽  
Tumor Cell Lines ◽  
Colon Tumor Cell

scholarly journals Src activation regulates anoikis in human colon tumor cell lines

Oncogene ◽  
2002 ◽  
Vol 21 (51) ◽  
pp. 7797-7807 ◽  
Author(s):  
T Christopher Windham ◽  
Nila U Parikh ◽  
Doris R Siwak ◽  
Justin M Summy ◽  
David J McConkey ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Colon ◽  
Colon Tumor ◽  
Tumor Cell Lines ◽  
Colon Tumor Cell ◽  
Src Activation

Influence of adenosine cyclic nucleotide analogs on growth of human colon tumor cell lines

Life Sciences ◽  
1990 ◽  
Vol 47 (4) ◽  
pp. 307-311 ◽  
Author(s):  
Michael V. Saba ◽  
David H. Barkla ◽  
Peter J.M. Tutton
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cyclic Nucleotide ◽  
Human Colon ◽  
Colon Tumor ◽  
Tumor Cell Lines ◽  
Nucleotide Analogs ◽  
Colon Tumor Cell

scholarly journals Preparation of Sesquiterpene Lactone Derivatives: Cytotoxic Activity and Selectivity of Action

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1113 ◽  
Author(s):  
María F. Beer ◽  
Augusto E. Bivona ◽  
Andrés Sánchez Alberti ◽  
Natacha Cerny ◽  
Guillermo F. Reta ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Biological Activities ◽  
Sesquiterpene Lactones ◽  
Chemotherapeutic Agents ◽  
Colon Tumor ◽  
Tumor Cell Lines ◽  
Diverse Range ◽  
Colon Tumor Cell

Cancer is one of the most important causes of death worldwide. Solid tumors represent the great majority of cancers (>90%) and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpene lactones are a group of naturally occurring compounds that have displayed a diverse range of biological activities including cytotoxic activity. A series of oxygenated and oxy-nitrogenated derivatives (4–15) from the sesquiterpene lactones cumanin (1), helenalin (2), and hymenin (3) were synthesized. The silylated derivatives of helenalin, compounds 13 and 14, were found to be the most active against tumor cell lines, with GI50 values ranging from 0.15 to 0.59 μM. The ditriazolyl cumanin derivative (11) proved to be more active and selective than cumanin in the tested breast, cervix, lung, and colon tumor cell lines. This compound was the least toxic against splenocytes (CC50 = 524.1 µM) and exhibited the greatest selectivity on tumor cell lines. This compound showed a GI50 of 2.3 µM and a SI of 227.9 on WiDr human colon tumor cell lines. Thus, compound 11 can be considered for further studies and is a candidate for the development of new antitumor agents.

Decreased Host-Cell Reactivation of UV-lrradiated Adenovirus in Human Colon Tumor Cell Lines that Have Normal Post-UV Survival

1999 ◽  
Vol 70 (2) ◽  
pp. 217-227
Author(s):  
Rufus S. Day ◽  
Aghdass Rasouli-Nia ◽  
James Meservy ◽  
Sibghat-Ullah Lari ◽  
Kelly Dobler ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Host Cell ◽  
Cell Lines ◽  
Human Colon ◽  
Colon Tumor ◽  
Tumor Cell Lines ◽  
Cell Reactivation ◽  
Colon Tumor Cell ◽  
Host Cell Reactivation
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