scholarly journals Nrf3 Promotes 5-FU Resistance in Colorectal Cancer Cells via the NF-κB/BCL-2 Signaling Pathway In Vitro and In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Bi-Qing Cai ◽  
Wan-Meng Chen ◽  
Jia Zhao ◽  
Wei Hou ◽  
Jian-Cai Tang
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Colon Cancer Cells ◽  
Tumor Drug Resistance ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
The Relationship

Increasing evidence indicates that nuclear factor, erythroid 2-like 3 (Nrf3) is connected with tumorigenesis. However, the relationship between Nrf3 and tumor drug resistance remains elusive. In this study, we investigated the effect and mechanism of action by which Nrf3 regulated the sensitivity of colon cancer cells to 5-fluorouracil (5-FU). We found Nrf3 was significantly increased in colon cancer tissues. Furthermore, we observed that Nrf3 knockdown and overexpression can significantly affect the sensitivity of colon cancer cells to 5-FU in vitro and in vivo. Moreover, Nrf3 promoted the expression of RELA, P-RELA, and BCL-2. Inhibition of NF-κB partly reversed the effects of Nrf3 overexpression, resulting in the resistance of colon cancer cells to 5-FU. Overall, the study revealed that Nrf3 was connected to the sensitivity of colon cancer cells to 5-FU, and its possible mechanism was related to the NF-κB signaling pathway, which provided a new target for overcoming the resistance of colon cancer cells to 5-FU.

scholarly journals Transgelin interacts with PARP1 in human colon cancer cells

2020 ◽  
Author(s):  
Zhen-xian Lew ◽  
Hui-min Zhou ◽  
Yuan-yuan Fang ◽  
Zhen Ye ◽  
Wa Zhong ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cellular Localization ◽  
Actin Binding ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Key Genes

Abstract Background: Transgelin, an actin-binding protein, is associated with cytoskeleton remodeling. Findings from our previous studies demonstrated that transgelin was up-regulated in node-positive colorectal cancer (CRC) versus 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 through which transgelin participates in the metastasis of colon cancer cells.Methods: Immunofluorescence and immunoblotting analysis were used to determine the cellular localization of endogenous and exogenous transgelin in colon cancer cells. Co-immunoprecipitation and subsequently high-performance liquid chromatography/tandem mass spectrometry were performed to identify the proteins that were potentially interacting with transgelin. The 256 downstream transcripts regulated by transgelin were analyzed with bioinformatics methods to discriminate the specific key genes and signaling pathways. The Gene-Cloud of Biotechnology Information (GCBI) tools were used to predict the potential transcription factors (TFs) for the key genes. The predicted TFs corresponded to the proteins identified to interact with transgelin. The interaction between transgelin and the TFs was verified by co-immunoprecipitation and immunofluorescence.Results: Transgelin was found to localize in both the cytoplasm and nucleus of the colon cancer cells. Approximately 297 proteins were identified to interact with transgelin. The overexpression of TAGLN led to the differential expression of 184 downstream genes. Network topology analysis discriminated seven genes, including CALM1, MYO1F, NCKIPSD, PLK4, RAC1, WAS and WIPF1 , which are mostly involved in the Rho signaling pathway. Poly (ADP-ribose) polymerase-1 (PARP1) was predicted as the unique TF for the key genes and concurrently corresponded to the DNA-binding proteins potentially interacting with transgelin. The interaction between PARP1 and transgelin in human RKO colon cancer cells was further validated by immunoprecipitation and immunofluorescence assays. Conclusions: Our results suggest that transgelin binds to PARP1 and regulates the expression of downstream key genes, which are mainly involved in the Rho signaling pathway, and thus participates in the metastasis of colon cancer.

scholarly journals FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenying Tian ◽  
Wenjia Zhang ◽  
Yan Zhang ◽  
Tianyue Zhu ◽  
Yuting Hua ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Akt Pathway ◽  
Colon Cancer Cells ◽  
Cancer Tissues ◽  
Adipose Tissue Extract

Abstract Background The prognosis of colon cancer is poor for metastasis, while the mechanism, especially adipocytes related, is not yet clear. The purpose of this study is to determine the effects of fatty acid binding protein 4 (FABP4), a transporter for lipids, on colon cancer progression. Methods The distribution of lipids and FABP4 was tested in the colon cancer tissues and adjacent normal tissues, and their relationship was also verified in vitro. Experiments about cellular invasion, migration and proliferation were performed to detect the impacts of FABP4 on the biological behaviors of colon cancer, and the positive results were checked in vivo. Meanwhile, the regulatory role of FABP4 in the energy and lipid metabolism was evaluated by the levels of triglyceride, ATP, LDH, glycerol and NEFA. At last, GO and KEGG analysis based on FABP4 overexpressed cells was performed, and the AKT pathway and epithelial–mesenchymal transition (EMT)-related proteins were determined by Western blot. Results Higher accumulation of lipids and stronger FABP4 transcription were observed in colon cancer tissues. Having been incubated with adipose tissue extract and overexpressed FABP4, colon cancer cells demonstrated enhanced lipid accumulation. In functional experiments, co-culture with adipose tissue extract significantly enhanced the invasion and migration of colon cancer cells, as well as the energy and lipid metabolism, and all these processes were reversed by FABP4 inhibitor. In addition, the metastasis of FABP4-overexpressed colon cancer cells was also significantly enhanced in vitro and in vivo. In terms of mechanism, the bioinformatics analysis showed that FABP4 was enriched in 11 pathways related to metabolic processes in FABP4 overexpressed cells. Finally, FABP4 overexpression improved EMT progression of colon cancer, as evidenced by the upregulation of Snail, MMP-2 and MMP-9, the downregulation of E-cadherin. The expression of p-Akt was also elevated. Conclusion FABP4 overexpression could increase FAs transport to enhance energy and lipid metabolism, and activate AKT pathway and EMT to promote the migration and invasion of 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.

932 Targeting the 19S Proteasomal Subunit, Rpt4, in Colon Cancer Cells Induces Cell Death and Reduces Cellular Proliferation In Vitro and In Vivo

2013 ◽  
Vol 144 (5) ◽  
pp. S-166-S-167
Author(s):  
Karen Boland ◽  
Caoimhin Concannon ◽  
Niamh McCawley ◽  
Elaine W. Kay ◽  
Deborah McNamara ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Colon Cancer Cells ◽  
Proliferation In Vitro

scholarly journals In Vitro and in Vivo antitumor activity and the mechanism of siphonodictyal B in human colon cancer cells

2019 ◽  
Vol 8 (12) ◽  
pp. 5662-5672 ◽  
Author(s):  
Sonoko Chikamatsu ◽  
Ken Saijo ◽  
Hiroo Imai ◽  
Koichi Narita ◽  
Yoshifumi Kawamura ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
In Vivo Antitumor Activity ◽  
Human Colon Cancer Cells

scholarly journals Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand

2020 ◽  
Author(s):  
Junhui Yu ◽  
Kui Yang ◽  
Jianbao Zheng ◽  
Wei Zhao ◽  
Xuejun Sun
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Farnesoid X Receptor ◽  
Colon Cancer Cells ◽  
Antitumor Effects ◽  
Colorectal Tumorigenesis ◽  
Tumor Inhibition ◽  
Combination Study

Abstract The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the importance of identifying drug combinations with potency and specificity to enhance the antitumor effects of FXR agonists. In this study, we found that the β-catenin level affected the antitumor effects of the FXR agonist OCA on colon cancer cells. Mechanistic studies identified a novel FXR/β-catenin complex in colon cancer cells. Furthermore, the depletion of β-catenin expedited FXR nuclear localization and enhanced its occupancy of the SHP promoter and thereby sensitized colon cancer cells to OCA. Furthermore, we utilized a drug combination study and identified that the antiparasitic drug nitazoxanide (NTZ) abrogated β-catenin expression and acted synergistically with OCA in colon cancer cells. The combination of OCA plus NTZ exerts synergistic tumor inhibition in CRC both in vitro and in vivo by cooperatively upregulating SHP expression. In conclusion, our study offers useful evidence for the clinical use of FXR agonists combined with β-catenin inhibitors in combating CRC.

scholarly journals NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Longgang Wang ◽  
Jinxiang Guo ◽  
Jin Zhou ◽  
Dongyang Wang ◽  
Xiuwen Kang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Tumor Models ◽  
Human Colon Cancer ◽  
Subcutaneous Tumor

Abstract Background Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer. Methods Tumor samples and matched normal samples were obtained from 35 colon cancer cases. CSCs were isolated from human colon cancer cell lines, where the stemness of the cells was evaluated by cell viability, colony-forming, spheroid-forming, invasion, migration, and apoptosis assays. NF-κB activation was then performed in subcutaneous tumor models of CSCs by injecting lipopolysaccharides (LPS) i.p. Results We found that NF-κB activation could reduce the expression of miR-195-5p and miR-497-5p, where these two miRNAs were determined to be downregulated in colon cancer tissues, cultured colon CSCs, and LPS-injected subcutaneous tumor models. Elevation of miR-195-5p and miR-497-5p levels by their specific mimic could ablate the effects of NF-κB on the stemness of colon cancer cells in vivo and in vitro, suggesting that NF-κB could maintain the stemness of colon cancer cells by downregulating miR-195-5p/497–5p. MCM2 was validated as the target gene of miR-195-5p and miR-497-5p in cultured colon CSCs. Overexpression of MCM2 was shown to restore the stemness of colon cancer cells in the presence of miR-195-5p and miR-497-5p, suggesting that miR-195-5p and miR-497-5p could impair the stemness of colon cancer cells by targeting MCM2 in vivo and in vitro. Conclusions Our work demonstrates that the restoration of miR-195-5p and miR-497-5p may be a therapeutic strategy for colon cancer treatment in relation to NF-κB activation.

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