Activation of Akt and MAPK pathways enhances the tumorigenicity of CD133+ primary colon cancer cells

Cancer stem cells (CSCs) play an important role in carcinogenesis, resistance to treatment and may lead to cancer recurrence and metastasis. However, the molecular mechanism of CSC involved in these events needs to be further elucidated. In this study, CD133+ colon cancer cells were cultured, which...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2010-08, Vol.31 (8), p.1376-1380
Main Authors: Wang, Y. K., Zhu, Y. L., Qiu, F. M., Zhang, T., Chen, Z. G., Zheng, S., Huang, J.
Format: Article
Language:English
Subjects:
AC133 Antigen
Animals
Antigens, CD - genetics
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Cell Division
Colonic Neoplasms - enzymology
Colonic Neoplasms - immunology
Colonic Neoplasms - metabolism
Colony-Forming Units Assay
Enzyme Activation
Flow Cytometry
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Glycoproteins - genetics
Humans
Medical sciences
Mice
Mice, Inbred NOD
Mice, SCID
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Oligonucleotide Array Sequence Analysis
Peptides - genetics
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Stem Cells - immunology
Stem Cells - pathology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Transplantation, Heterologous
Tumor Cells, Cultured
Tumors
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Summary:Cancer stem cells (CSCs) play an important role in carcinogenesis, resistance to treatment and may lead to cancer recurrence and metastasis. However, the molecular mechanism of CSC involved in these events needs to be further elucidated. In this study, CD133+ colon cancer cells were cultured, which showed CSC properties both in vitro and in vivo from metastatic tissue. Upstream molecules in Akt and mitogen-activated protein kinase (MAPK) pathways were preferentially expressed in these CD133+ cells, as revealed by a global gene chip. The kinase activities of Akt and extracellular signal-regulated kinase (Erk)1/2 were also significantly upregulated in CD133+ cells. In addition, the clonogenic growth of CD133+ cell was reduced greatly by inhibiting the activity of Akt and Erk1/2. The results revealed the Akt and MAPK pathways were involved in the tumorigenesis of CD133+ colon cancer cells, suggesting that molecules in these two pathways might be potential targets in the future therapy.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgq120