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Atonal homolog 1 protein stabilized by tumor necrosis factor α induces high malignant potential in colon cancer cell line.

Fukushima K, Tsuchiya K, Kano Y, Horita N, Hibiya S, Hayashi R, Kitagaki K, Negi M, Itoh E, Akashi T, Eishi Y, Oshima S, Nagaishi T, Okamoto R, Nakamura T, Watanabe M - Cancer Sci. (2015)

Bottom Line: We have previously reported that the proteasomal degradation of the transcription factor Atonal homolog 1 (Atoh1) protein results in the non-mucinous form of CRC.Consequently, the treatment with TNF-α stabilized Atoh1 protein through the inactivation of GSK-3β via Akt, resulting in the mucinous form of CRC cell lines.In conclusion, the inflammation associated with carcinogenesis may preserve the differentiation system of intestinal epithelial cell (IEC), resulting in the acquisition of both the mucinous phenotype and high malignant potential associated with the enrichment of cancer stem cell.

View Article: PubMed Central - PubMed

Affiliation: Departments of Gastroenterology and Hepatology, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.

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Stable expression of Atonal homolog 1 (Atoh1) protein by TNF-α promotes cell migration. (a) Migration assay showed that the vacant area was occupied by a greater number of Atoh1-DLD1 cells cultured with TNF-α for 20 weeks than the others. Scale bar, 500 μm. (b) The ratio of the remaining vacant area is shown. The vacant area of Atoh1-DLD1 cells was smaller than that of others at 24 h after the cells were seeded. ***P < 0.001, n = 6. (c) The expression of ZEB1 in DLD1 cells was analyzed by RT-PCR. ZEB1 gene was significantly upregulated in Atoh1-DLD1 cells with TNF-α treatment for 20 weeks. **P < 0.01, ***P < 0.001, n = 3.
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fig04: Stable expression of Atonal homolog 1 (Atoh1) protein by TNF-α promotes cell migration. (a) Migration assay showed that the vacant area was occupied by a greater number of Atoh1-DLD1 cells cultured with TNF-α for 20 weeks than the others. Scale bar, 500 μm. (b) The ratio of the remaining vacant area is shown. The vacant area of Atoh1-DLD1 cells was smaller than that of others at 24 h after the cells were seeded. ***P < 0.001, n = 6. (c) The expression of ZEB1 in DLD1 cells was analyzed by RT-PCR. ZEB1 gene was significantly upregulated in Atoh1-DLD1 cells with TNF-α treatment for 20 weeks. **P < 0.01, ***P < 0.001, n = 3.

Mentions: We assessed whether Atoh1 promotes cell migration. Atoh1 protein stabilization by TNF-α promoted cell migration, whereas the treatment with TNF-α alone in mock DNA-expressing DLD1 cells did not change cell migration (Fig.4a,b).


Atonal homolog 1 protein stabilized by tumor necrosis factor α induces high malignant potential in colon cancer cell line.

Fukushima K, Tsuchiya K, Kano Y, Horita N, Hibiya S, Hayashi R, Kitagaki K, Negi M, Itoh E, Akashi T, Eishi Y, Oshima S, Nagaishi T, Okamoto R, Nakamura T, Watanabe M - Cancer Sci. (2015)

Stable expression of Atonal homolog 1 (Atoh1) protein by TNF-α promotes cell migration. (a) Migration assay showed that the vacant area was occupied by a greater number of Atoh1-DLD1 cells cultured with TNF-α for 20 weeks than the others. Scale bar, 500 μm. (b) The ratio of the remaining vacant area is shown. The vacant area of Atoh1-DLD1 cells was smaller than that of others at 24 h after the cells were seeded. ***P < 0.001, n = 6. (c) The expression of ZEB1 in DLD1 cells was analyzed by RT-PCR. ZEB1 gene was significantly upregulated in Atoh1-DLD1 cells with TNF-α treatment for 20 weeks. **P < 0.01, ***P < 0.001, n = 3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556389&req=5

fig04: Stable expression of Atonal homolog 1 (Atoh1) protein by TNF-α promotes cell migration. (a) Migration assay showed that the vacant area was occupied by a greater number of Atoh1-DLD1 cells cultured with TNF-α for 20 weeks than the others. Scale bar, 500 μm. (b) The ratio of the remaining vacant area is shown. The vacant area of Atoh1-DLD1 cells was smaller than that of others at 24 h after the cells were seeded. ***P < 0.001, n = 6. (c) The expression of ZEB1 in DLD1 cells was analyzed by RT-PCR. ZEB1 gene was significantly upregulated in Atoh1-DLD1 cells with TNF-α treatment for 20 weeks. **P < 0.01, ***P < 0.001, n = 3.
Mentions: We assessed whether Atoh1 promotes cell migration. Atoh1 protein stabilization by TNF-α promoted cell migration, whereas the treatment with TNF-α alone in mock DNA-expressing DLD1 cells did not change cell migration (Fig.4a,b).

Bottom Line: We have previously reported that the proteasomal degradation of the transcription factor Atonal homolog 1 (Atoh1) protein results in the non-mucinous form of CRC.Consequently, the treatment with TNF-α stabilized Atoh1 protein through the inactivation of GSK-3β via Akt, resulting in the mucinous form of CRC cell lines.In conclusion, the inflammation associated with carcinogenesis may preserve the differentiation system of intestinal epithelial cell (IEC), resulting in the acquisition of both the mucinous phenotype and high malignant potential associated with the enrichment of cancer stem cell.

View Article: PubMed Central - PubMed

Affiliation: Departments of Gastroenterology and Hepatology, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus