• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.531-535
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• 2015

Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern of embryonic vasculogenesis, which was associated with invasion and metastasis. The grape seed proanthocyanidins (GSPs) had attracted much attention as a potential bioactive anti-carcinogenic agent. However, GSPs regulation of VM and its possible mechanisms in a triple-negative breast cancer cells (TNBCs) remain not clear. Therefore, we examined the effect of GSPs on VM information in HCC1937 cell model. In this study, we identified the VM structure via the three-dimensional (3D) matrix in vitro. Cell viability was measured using the CCK8 assay. The effects of GSPs on human triple-negative breast cancer cells (TNBCs) HCC1937 in terms of related proteins of VM information were determined using western blot analysis. In vitro, the tubular networks were found in highly invasive HCC1937 cells but not in the non-invasive MCF-7 cells when plated on matrigel. The number of vascular channels was significantly reduced when cells were exposed in GSPs ($100{\mu}g$/ml) and GSPs ($200{\mu}g/mL$) groups (all p<0.001). Furthermore, we found that treatment with GSPs promoted transition of the mesenchymal state to the epithelial state in HCC1937 cells as well as reducing the expression of Twist1 protein, a master EMT regulator.GSPs has the ability to inhibit VM information by the suppression of Twist1 protein that could be related to the reversal of epithelial-to-mesenchymal (EMT) process. It is firstly concluded that GSPs may be an p otential anti-VM botanical agent for human TNBCs.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.669-672
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• 2013

Objective: To investigate the expression of Twist and E-cadherin in ovarian cancer tissues as well as the role of epithelial-mesenchymal transformation (EMT) in ovarian cancer metastasis. Method: The expressions of Twist and E-cadherin in 54 cases of ovarian cancer and paracancerous tissues were detected by Western blottin g and reverse transcriptase polymerase chain reaction. We used RNA interference to silence Twist expression in human ovarian cancer cell line, and detected E-cadherin expression using Western blotting. Results: There was an increase in the relative abundance of Twist proteins and a decrease in E-cadherin in ovarian cancer compared with normal ovary tissues (P < 0.05). The expression levels of Twist and E-cadherin mRNA were $1.49{\pm}0.53$ and $0.82{\pm}0.24$ in ovarian cancer, and $1.14{\pm}0.38$ and $1.08{\pm}0.19$ in paracancerous tissues, respectively. The difference between the indicators in ovarian cancer and in paracancerous tissues was statistically significant (P < 0.05). When the Twist expression was silenced in an ovarian cancer cell line, the expression of the E-cadherin protein increased (P<0.05). Conclusion: The expression of Twist is upregulated, whereas that of E-cadherin is downregulated in ovarian cancer. EMT, mediated by Twist, may be correlated with ovarian cancer metastasis.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.380-388
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• 2022

Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.391-396
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• 2014

Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3987-3989
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• 2013

This is a commentary on what a cancer cell is and why cancer cells metastasize. Normal cell get transformed to a cancer cell, with excessive production of free radicals that mutate the DNA of a normal cell. The immortality and malignant stage of transformed cell is maintained by higher GSH levels. With the faster rate of proliferation, when the cancer cell finds the place of origin is not conducive to its further growth, cancer cell chooses to take the metastatic course. We argue that if we can stop the exit of cancer cell from place of origin, cancer spread can be stopped or even cured.

• BMB Reports
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• 제48권4호
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• pp.217-222
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• 2015

Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death worldwide. Distant metastasis is a major cause of mortality in CRC. MicroRNAs (miRNAs) are small non-coding RNA molecules involved in the post-transcriptional and translational regulation of gene expression. Many miRNAs are aberrantly expressed in cancer and influence tumor progression. Accumulating studies suggest that multiple miRNAs are actively involved in the CRC metastasis process. Thus, we aim to introduce the role of miRNAs in multi-steps of CRC metastasis, including cancer cell invasion, intravasation, circulation, extravasation, colonization, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, we suggest the potential application of miRNAs as biomarkers for CRC patients with metastasis. [BMB Reports 2015; 48(4): 217-222]

• Archives of Plastic Surgery
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• 제45권6호
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• pp.600-601
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• 2018

• International Journal of Industrial Entomology and Biomaterials
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• 제34권1호
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• pp.1-5
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• 2017

Bone morphogenetic protein 2 (BMP2) plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is involved also in cardiac cell differentiation and epithelial to mesenchymal transition. In this study, We expressed human BMP2 (hBMP2) recombinant protein using Baculovirus Expression Vector System (BEVS) in Sf9 insect cells. The hBMP2 cDNA was cloned into baculovirus transfer vector, pBacgus-4x-1 and recombinant baculovirus was screened out through X-gal and GUS-fusions assay. Western blot analysis shown that molecular weight of hBMP2 recombinant protein was about 44.71 kDa.

• 대한의생명과학회지
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• 제24권4호
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• pp.285-291
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• 2018

Gremlin-1 (GREM1) has been defined as an antagonist of bone morphogenetic proteins (BMPs), particularly during embryonic development and tissue differentiation. However, recent studies have shown that GREM1 has BMPs-dependent or -independent functions in diverse human diseases. GREM1 plays a key role in the process of organ fibrosis, including lungs, kidneys, and so on. The GREM1-induced fibrosis typically promotes the development of other diseases, such as pulmonary hypertension, renal inflammation, and diabetic nephropathy. More recently, considerable evidence has been reported showing that GREM1 is involved in the promotion and/or progression of tumors in vitro and in vivo. It also performs an oncogenic role in the maintenance of cancer stem cells. Although GREM1 is known to function in a variety of diseases, here we focus on the role of GREM1 in cancer, and suggest GREM1 as a potential therapeutic target in certain types of cancer.

• BMB Reports
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• 제56권7호
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• pp.410-415
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• 2023

Breast cancer has become the most common cancer among women worldwide. Among breast cancers, metastatic breast cancer is associated with the highest mortality rate. Twist1, one of the epithelial-mesenchymal transition-regulating transcription factors, is known to promote the intravasation of breast cancer cells into metastatic sites. Therefore, targeting Twist1 to develop anti-cancer drugs might be a valuable strategy. In this study, LY-290181 dose-dependently inhibited migration, invasion, and multicellular tumor spheroid invasion in breast cancer cell lines. These anti-cancer effects of LY-290181 were mediated through the down-regulation of Twist1 protein levels. LY-290181 inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways. Therefore, our findings suggest that LY-290181 may serve as a basis for future research and development of an anti-cancer agent targeting metastatic cancers.