scholarly journals CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Lin-Lin Lu ◽  
Xiao-Hui Chen ◽  
Ge Zhang ◽  
Zong-Cai Liu ◽  
Nong Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Mrna Levels ◽  
Stem Cell Property ◽  
Mammosphere Formation ◽  
Cell Property ◽  
Gsk 3Β ◽  
Hct116 Cells

Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp) and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC) HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3βmediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients.

scholarly journals Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Guang-Yuh Chiou ◽  
Tzu-Wei Yang ◽  
Chi-Chou Huang ◽  
Chia-Ying Tang ◽  
Jung-Yi Yen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Cell Lineage ◽  
Stem Cell Lineage ◽  
Colorectal Cancer Cells

scholarly journals Endothelial cells activate the cancer stem cell-associatedNANOGP8pathway in colorectal cancer cells in a paracrine fashion

2017 ◽  
Vol 11 (8) ◽  
pp. 1023-1034 ◽  
Author(s):  
Rui Wang ◽  
Rajat Bhattacharya ◽  
Xiangcang Ye ◽  
Fan Fan ◽  
Delphine R. Boulbes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Colorectal Cancer Cells

scholarly journals Inhibitory effect of selenomethionine on carcinogenesis in the model of human colorectal cancer in vitro and its link to the Wnt/β-catenin pathway.

2018 ◽  
Vol 65 (3) ◽  
Author(s):  
Edyta Korbut ◽  
Agata Ptak-Belowska ◽  
Tomasz Brzozowski
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Colorectal Carcinogenesis ◽  
Mrna Levels ◽  
Human Colorectal Cancer ◽  
Bax Protein ◽  
Colorectal Cancer Cells ◽  
Gsk 3Β ◽  
Ht 29

Selenium compounds have been implicated as anticancer agents; however, the mechanism of their inhibitory action against cancer development has not been extensively investigated. The constitutive activation of the Wnt/β-catenin pathway is a central event in colorectal carcinogenesis. In this pathway, the excessive cell proliferation is initiated by the generation of β-catenin followed by overexpression of proto-oncogenes such as c-Myc. It is believed that under physiological conditions the level of c-Myc is efficiently controlled by accessibility of β-catenin protein through the process of phosphorylation by glycogen synthase kinase 3β (GSK-3β). Here, we determined whether selenomethionine (SeMet) can inhibit cell growth and affect the Wnt/β-catenin pathway in HT-29 human colorectal cancer cells in vitro. The effective cytotoxic doses of SeMet have been selected after 48 h of incubation of this compound with colorectal cancer HT-29 cell line. The MTT assay was used to assess cell viability and the protein and mRNA levels of β-catenin and c-Myc were determined by Western blotting and qPCR, respectively. The SeMet potently inhibited growth of HT-29 cells, significantly decreased the β-catenin protein and mRNA concentration, down-regulated the c-Myc gene expression and up-regulated pro-apoptotic Bax protein expression. Moreover, SeMet increased the level of GSK-3β phosphorylated at serine 9 (S9) and significantly increased the level of β-catenin phosphorylated at S33 and S37. We conclude that SeMet suppresses the growth of HT-29 colorectal cancer cells by the mechanism linked to the Wnt/β-catenin pathway, however, the degradation of β-catenin may occur independently of GSK-3β catalytic activity and its phosphorylation status.

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