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 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.
Wang
Y K
YK
Cancer Institute, Zhejiang University School of Medicine, Hangzhou, China.
Zhu
Y L
YL
Qiu
F M
FM
Zhang
T
T
Chen
Z G
ZG
Zheng
S
S
Huang
J
J
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002455:Cell Division; D003110:Colonic Neoplasms / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D004789:Enzyme Activation; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases