scholarly journals HomeoboxC6 promotes metastasis by orchestrating the DKK1/Wnt/β-catenin axis in right-sided colon cancer

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Lina Qi ◽  
Jiani Chen ◽  
Biting Zhou ◽  
Kailun Xu ◽  
Kailai Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Poor Prognosis ◽  
Migration And Invasion ◽  
Tumor Proliferation ◽  
Colon Cancer Cells ◽  
Ht29 Cells ◽  
Proliferation And Metastasis ◽  
Tumor Proliferation And Metastasis

AbstractPatients with right-sided colon cancer (RCC) generally have a poorer prognosis than those with left-sided colon cancer (LCC). We previously found that homeobox C6 (HOXC6) was the most significantly upregulated gene in RCC compared to LCC. However, it remains unclear whether HOXC6 plays a role in tumor proliferation and metastasis. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in RCC. In this study, HOXC6 was validated to be overexpressed in RCC and associated with poor prognosis. Furthermore, overexpression of HOXC6 promoted the migration and invasion of colon cancer cells through inducing EMT by activating the Wnt/β-catenin signaling pathway and inhibition of DKK1 secretion. Lastly, we preliminary explored the translational effect of HOXC6 and found that silencing of HOXC6 made HCT116 and HT29 cells more sensitive to irinotecan.

scholarly journals HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

2019 ◽  
Author(s):  
Na Li ◽  
Jiao Xiong ◽  
Zhengyu Li
Keyword(s):  
Ovarian Cancer ◽  
Poor Prognosis ◽  
Malignant Progression ◽  
Stem Cell Markers ◽  
Tumor Proliferation ◽  
The Poor ◽  
Proliferation And Metastasis ◽  
Proliferation And Invasion ◽  
Tumor Proliferation And Metastasis

Abstract Background: Homeobox B4 (HOXB4) is associated with the poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains to be determined. Methods：The Cancer Genome Atlas (TCGA) database indicated that high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed through a colony formation, migration, and invasion assay. The effect of HOXB4 on the expression of EMT and cancer stem cell markers was detected. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was performed in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results：Results showed that the expression of HOXB4 was higher in OV tissues than in normal tissues and correlated with the poor prognosis of OV. HOXB4 knockdown suppressed the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the up-regulation of HOXB4 in OV cells. The binding of two DNA motifs through HOXB4 regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in promoting tumor proliferation and metastasis was verified in mice. Further investigation revealed that HOXB4 triggered Snail and Zeb1 expression. Conclusion: Overall, HOXB4 overexpression was remarkably correlated with the poor prognosis of OV. HOXB4 up-regulated DHDDS, which co-contributed to the enhancer proliferation and invasion of OV cells, thus accelerating the malignant progression of OV.

scholarly journals Autumn Royal and Ribier Grape Juice Extracts Reduced Viability and Metastatic Potential of Colon Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Manuel Valenzuela ◽  
Lorena Bastias ◽  
Iván Montenegro ◽  
Enrique Werner ◽  
Alejandro Madrid ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Grape Juice ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Gene Expressions ◽  
Anticancer Properties

Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type.Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells.

scholarly journals Differential Mechanism of ATP Production Occurs in Response to Succinylacetone in Colon Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3575 ◽  
Author(s):  
Lee ◽  
Woo ◽  
Yoo ◽  
Cho ◽  
Kim
Keyword(s):  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Oxygen Species ◽  
Colon Cancer Cells ◽  
Atp Production ◽  
Ht29 Cells ◽  
Differential Mechanism ◽  
Hct116 Cells

Our aim was to verify the potential ability of succinylacetone (SA) to inhibit mitochondrial function, thereby suppressing cancer cell proliferation. SA treatment caused apoptosis in HCT116 and HT29 cells, but not in SW480 cells, with mitochondria playing a key role. We checked for dysfunctional mitochondria after SA treatment. Mitochondria of HT29 cells were swollen, indicating damage, whereas in HCT116 cells, several mitochondria had a diminished size. Damaged mitochondria decreased ATP production and induced reactive oxygen species (ROS) in the cells. To understand SA-induced reduction in ATP production, we investigated the electron transfer chains (ETC) and pyruvate dehydrogenase kinase (PDK) activity, which prevents the transfer of acetyl-CoA to the TCA (tricarboxylic acid) cycle by inhibiting PDH (pyruvate dehydrogenase) activity. In each cell line, the inhibitory mechanism of ATP by SA was different. The activity of complex III consisting of the mitochondrial ETCs in HT29 cells was decreased. In contrast, PDH activity in HCT116 cells was reduced. Nicotinamide nucleotide transhydrogenase (NNT)-removing reactive oxygen species (ROS) was upregulated in HT29 cells, but not in HCT116 cells, indicating that in HT29 cells, a defense mechanism was activated against ROS. Collectively, our study showed a differential mechanism occurs in response to SA in colon cancer cells.

scholarly journals Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Jiafeng Tong ◽  
Ying Shen ◽  
Zhenghua Zhang ◽  
Ye Hu ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Human Colon Cancer Cells

Abstract Colon cancer is a leading cause of cancer-related deaths worldwide. The epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis of colon cancer. We first evaluated the effects of EMT-related transcription factors on the prognosis of colon cancer through analysis the data obtained from The Cancer Genome Atlas (TCGA). And then we screened a series of Chinese medicine monomers to find effect EMT inhibitors. First, Snail is a more important EMT transcription factors for colon cancer prognosis, compared with Twist and Slug. Then, we found that apigenin effectively inhibits the activity of Snail. Apigenin could inhibit the EMT, migration, and invasion of human colon cancer cells in vitro and in vivo through the NF-κB/Snail pathway. Snail is a key regulator of EMT in colon cancer and Snail inhibitor apigenin may be a therapeutic application for patients with colon cancer.

scholarly journals PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengbin Chai ◽  
Li Wang ◽  
Yabing Zheng ◽  
Na Liang ◽  
Xiwei Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Expression Pattern ◽  
Colony Formation ◽  
Regulatory Mechanism ◽  
Cancer Cell Proliferation ◽  
Colon Cancer Cells ◽  
Cancer Tissues

Abstract Background CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research. Methods Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo. Results CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells. Conclusions PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.

scholarly journals GLUT5 regulation by AKT1/3-miR-125b-5p downregulation induces migratory activity and drug resistance in TLR-modified colorectal cancer cells

2020 ◽  
Vol 41 (10) ◽  
pp. 1329-1340 ◽  
Author(s):  
Ga-Bin Park ◽  
Jee-Yeong Jeong ◽  
Daejin Kim
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cell Metabolism ◽  
Enzyme Activation ◽  
Migration And Invasion ◽  
Drug Resistant ◽  
Cancer Resistance ◽  
Colon Cancer Cells ◽  
Migratory Activity

Abstract In cancer, resistance to chemotherapy is one of the main reasons for therapeutic failure. Cells that survive after treatment with anticancer drugs undergo various changes, including in cell metabolism. In this study, we investigated the effects of AKT-mediated miR-125b-5p alteration on metabolic changes and examined how these molecules enhance migration and induce drug resistance in colon cancer cells. AKT1 and AKT3 activation in drug-resistant colon cancer cells caused aberrant downregulation of miR-125b-5p, leading to GLUT5 expression. Targeted inhibition of AKT1 and AKT3 restored miR-125b-5p expression and prevented glycolysis- and lipogenesis-related enzyme activation. In addition, restoring the level of miR-125b-5p by transfection with the mimic sequence not only significantly blocked the production of lactate and intracellular fatty acids but also suppressed the migration and invasion of chemoresistant colon cancer cells. GLUT5 silencing with small interfering RNA attenuated mesenchymal marker expression and migratory activity in drug-resistant colon cancer cells. Additionally, treatment with 2,5-anhydro-d-mannitol resensitized chemoresistant cancer cells to oxaliplatin and 5-fluorouracil. In conclusion, our findings suggest that changes in miR-125b-5p and GLUT5 expression after chemotherapy can serve as a new marker to indicate metabolic change-induced migration and drug resistance development.

scholarly journals Cancer Preventive Effect of a Novel High Phenolic Sorghum Bran on Human Colon Cancer Cells (P05-008-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Seong-Ho Lee ◽  
Jihye Lee ◽  
Thomas Herald ◽  
Sarah Cox ◽  
Leela Noronha ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Citric Acid ◽  
Cancer Cells ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Sorghum Bran ◽  
Human Colon Cancer Cells

Abstract Objectives Colon cancer is one of leading causes of cancer mortality worldwide. Sorghum is the fifth most largely cultivated crop for human diet in the world. Most sorghum varieties contain high content of phenolic compounds. The objective of the current study is to evaluate the anti-cancer properties of a novel high phenolic sorghum bran extract prepared under 70% ethanol with 5% citric acid solvent. Methods High phenolic sorghum, accession number PI570481, was grown in Puerto Vallarta, Mexico winter nursery during the 2018 and high phenolic sorghum bran extract was prepared using 70% ethanol with 5% citric acid solvent at room temperature for 2 hours. Human colon cancer cell lines (HCT15, SW480, HCT116 and HT-29) were treated with different doses of high phenolic sorghum bran extract. Cell proliferation and apoptosis was measured using MTS assay and Alexa Fluor 488 Annexin V/Dead Cell Apoptosis system, respectively. Distribution of cell cycle was measured Texas Red channel using BD LSRFortessa system. Cell migration and invasion was measured using wound healing assay and Matrigel, respectively. The luciferase activity of reporter genes was measured using a dual-luciferase assay and Western blot was performed to measure expression of cancer phenotype-associated proteins. Results Cell proliferation was inhibited and apoptosis was induced in the human colon cancer cells treated with high phenolic sorghum bran extract in a dose-dependent manner. High phenolic sorghum bran extract led to S phage arrest. Cell migration and invasion was also repressed in the human colon cancer cells treated with high phenolic sorghum bran extract. The change of cancer phenotypes was associated with up- or down-regulation of regulatory genes. Conclusions The present study expands our understanding on the potential use of high phenolic sorghum bran for prevention of human colon cancer. Funding Sources Cooperative Agreement grant from USDA-ARS to S-HL.

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