scholarly journals Exosomes Derived from SW480-Resistant Colon Cancer Cells are Promote Angiogenesis via BMP-2/Smad5 Signaling Pathway

2021 ◽  
Author(s):  
Song Yang ◽  
Lei Yao ◽  
Xiaolong Wang ◽  
Hao Sun ◽  
Chaogang Du ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Colon Cancer Cells ◽  
Promoting Effect ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Abstract Background: Multidrug resistance is the main cause of tumor recurrence and metastasis. Therefore, it is urgent to explore the mechanism and treatment of drug resistance of tumor cells. We aim to investigate the relationship between drug resistance and angiogenesis in SW480 colon cancer cells, and the possible underlying mechanism.Methods: Exosomes was extracted from SW480-sensitive or -resistant colon cancer cells (SW480/Oxaliplatin). MTT assay, migration assay, tube formation assay, qPCR and Western blotting were performed in human umbilical vein endothelial cells (HUVECs).Results: The conditioned medium and exosomes of SW480/Oxaliplatin cells promoted proliferation, migration, and tube formation of HUVECs. The expression of BMP-2 in SW480/Oxaliplatin exosomes was 2.3 folds higher than that in SW480 exosomes. BMP-2 promoted angiogenesis in vitro by inhibiting the Smad signaling pathway. Moreover, TGF-β1, an activator of the Smad signaling pathway, could partly block the promoting effect of SW480/Oxaliplatin exosomes on angiogenesis.Conclusions: SW480 resistant colon cancer exosomes promoted angiogenesis via inhibiting the BMP-2/Smad signaling pathway.

scholarly journals Betulinic Acid Inhibits the Metastasis of Colon Cancer Cells through Regulating TGF-β/Smad Signaling Pathway

2020 ◽  
Vol 30 (1) ◽  
pp. 58-63
Author(s):  
晓英 林 ◽  
阿灵 沈 ◽  
美珠 吴 ◽  
瑛 程 ◽  
晓萍 陈 ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Betulinic Acid ◽  
Colon Cancer Cells ◽  
Tgf Beta ◽  
Smad Signaling ◽  
Smad Signaling Pathway

scholarly journals Cancer upregulated gene 2, a novel oncogene, enhances migration and drug resistance of colon cancer cells via STAT1 activation

2013 ◽  
Vol 43 (4) ◽  
pp. 1111-1116 ◽  
Author(s):  
WARAPORN MALILAS ◽  
SANG SEOK KOH ◽  
SEOKHO KIM ◽  
RATAKORN SRISUTTEE ◽  
IL-RAE CHO ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Colon Cancer Cells

scholarly journals ADCK1 activates the β-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yong Ji ◽  
Yiqian Liu ◽  
Changchun Sun ◽  
Lijiang Yu ◽  
Zhao Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Activation Mechanism ◽  
Colon Cancer Cells ◽  
Mechanistic Studies ◽  
T Cell Factor ◽  
And Migration

AbstractAs a result of mutations in the upstream components of the Wnt/β-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the β-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.

scholarly journals Transforming Growth Factor β Mediates Drug Resistance by Regulating the Expression of Pyruvate Dehydrogenase Kinase 4 in Colorectal Cancer

2016 ◽  
Vol 291 (33) ◽  
pp. 17405-17416 ◽  
Author(s):  
Yang Zhang ◽  
Yi Zhang ◽  
Liying Geng ◽  
Haowei Yi ◽  
Wei Huo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Mouse Xenograft Model

Drug resistance is one of the main causes of colon cancer recurrence. However, our understanding of the underlying mechanisms and availability of therapeutic options remains limited. Here we show that expression of pyruvate dehydrogenase kinase 4 (PDK4) is positively correlated with drug resistance of colon cancer cells and induced by 5-fluorouracil (5-FU) treatment in drug-resistant but not drug-sensitive cells. Knockdown of PDK4 expression sensitizes colon cancer cells to 5-FU or oxaliplatin-induced apoptosis in vitro and increases the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. In addition, we demonstrate for the first time that TGFβ mediates drug resistance by regulating PDK4 expression and that 5-FU induces PDK4 expression in a TGFβ signaling-dependent manner. Mechanistically, knockdown or inhibition of PDK4 significantly increases the inhibitory effect of 5-FU on expression of the anti-apoptotic factors Bcl-2 and survivin. Importantly, studies of patient samples indicate that expression of PDK4 and phosphorylation of Smad2, an indicator of TGFβ pathway activation, show a strong correlation and that both positively associate with chemoresistance in colorectal cancer. These findings indicate that the TGFβ/PDK4 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of PDK4 may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, which warrants the development of PDK4-specific inhibitors.

scholarly journals Transgelin interacts with PARP1 and affects Rho signaling pathway in human colon cancer cells

2020 ◽  
Author(s):  
Zhen-xian Lew ◽  
Hui-min Zhou ◽  
Yuan-yuan Fang ◽  
Zhen Ye ◽  
Wa Zhong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Colon Cancer ◽  
Transcription Factor ◽  
High Performance Liquid Chromatography ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
High Performance ◽  
Colon Cancer Cells ◽  
Over Expression ◽  
Key Genes

Abstract Background: Transgelin, an actin-binding protein, is associated with the cytoskeleton remodeling. Our previous studies found that transgelin was up-regulated in node-positive colorectal cancer versus in node-negative disease. Over-expression of TAGLN affected the expression of 256 downstream transcripts and increased the metastatic potential of colon cancer cells in vitro and in vivo. This study aims to explore the mechanisms that transgelin participates in the metastasis of colon cancer cells.Methods: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of the endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequent high performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins potentially interacting with transgelin. Bioinformatics methods were used to analyze the 256 downstream transcripts regulated by transgelin to discriminate the specific key genes and signaling pathways. By analyzing the promoter region of these key genes, GCBI tools were used to predict the potential transcription factor(s) for these genes. The predicted transcription factors were matching to the proteins that have been identified to potentially interact with transgelin. The interaction between transgelin and these transcription factors was verified by co-immunoprecipitation and immunoblotting.Results: Transgelin was found to localize both in the cytoplasm and the nucleus of colon cancer cells. 297 proteins have been identified to interact with transgelin by co-immunoprecipitation and subsequent high performance liquid chromatography/mass spectrometry. Over-expression of TAGLN could lead to differential expression of 184 downstream genes. By constructing the network of gene-encoded proteins, 7 genes (CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1) have been discriminated as key genes using network topology analysis. They are mostly involved in the Rho signaling pathway. Poly ADP-ribose polymerase-1 (PARP1) was predicted as the unique transcription factor for the key genes and concurrently matching to the DNA-binding proteins potentially interacting with transgelin. Immunoprecipitation validated that PARP1 interacted with transgelin in human RKO colon cancer cells.Conclusions: The results of this study suggest that transgelin binds to PARP1 and regulates the expression of the downstream key genes mainly involving Rho signaling pathway, thus participates in the metastasis of colon cancer.

scholarly journals β1, 4-N-acetylgalactosaminyltransferase III modulates cancer stemness through EGFR signaling pathway in colon cancer cells

Oncotarget ◽  
2014 ◽  
Vol 5 (11) ◽  
pp. 3673-3684 ◽  
Author(s):  
Mei-Ieng Che ◽  
John Huang ◽  
Ji-Shiang Hung ◽  
Yo-Chuen Lin ◽  
Miao-Juei Huang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Colon Cancer Cells ◽  
Egfr Signaling ◽  
Cancer Stemness ◽  
Egfr Signaling Pathway
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