Cancer Institute, Zhejiang University School of Medicine, Hangzhou, China.
Carcinogenesis. 2010 Aug;31(8):1376-80. doi: 10.1093/carcin/bgq120. Epub 2010 Jun 8.
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.
癌症干细胞（CSC）在肿瘤发生、治疗耐药中发挥重要作用，并可能导致癌症复发和转移。然而，CSC 参与这些事件的分子机制尚需进一步阐明。本研究培养了 CD133(+)结肠癌细胞，这些细胞在体外和转移组织的体内均表现出 CSC 特性。通过全基因芯片发现，Akt 和丝裂原活化蛋白激酶（MAPK）通路中的上游分子在这些 CD133(+)细胞中优先表达。Akt 和细胞外信号调节激酶（Erk）1/2 的激酶活性在 CD133(+)细胞中也显著上调。此外，通过抑制 Akt 和 Erk1/2 的活性，CD133(+)细胞的集落生长大大减少。结果表明 Akt 和 MAPK 通路参与了 CD133(+)结肠癌细胞的肿瘤发生，提示这两条通路中的分子可能是未来治疗的潜在靶点。
