Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway

Cancer Cell, vol. 5 April 2004

Speaker : 吳 鳳 翎                     Commentator :劉校生 老師

Time: 14:00~15:00 ;October 27,2004              Place: Room : 601

Abstract:

Colon cancer is the second leading cause of death from malignancy in the United States (1). It is also the most common type of tumor to metastasize to the liver. Metastasis has been the major cause of death in colon cancer, the effective treatment of colon cancer become a difficult goal to achieve. The authors found a gene, periostin, which is upregulated during metastasis. Periostin is a secreted protein that isolated from osteoblasts and found to be preferentially expressed in periosteum in bone tissue (2). Expression of Periostin in colon cancer is associated with enhanced tumor metastastic growth and angiogenesis result from promoting survival for both cancer cell and endothelial cells. The cancer cells are subcutaneously injected into nude mice to prove the potential effect of periostin on tumor growth. Strikingly, multiple large tumor metastases were detected after the intra-splenic injection of cancer cells proving periostin plays an important role in tumor metastasis. All metastasis derived from periostin producing cells displayed a high levels of hemorrhaging, suggesting elevated degrees of vascularization. Actually, periostin mRNA is overexpressed in almost cases of colon metastatic tumors in the liver metastates. Overexpression of periostin in colon cancer cells lead to higher level of cellular survival or a less content of apoptosis that favors metastases development in vivo and dramatically lead to tumor metastasis in the liver. The molecular mechanism that periostin promotes cell survival is associated with α_vβ₃ integrin and Akt/PKB pathway (3).These results indicating that periostin could serve as a potential target in therapy of colon cancer in the future.

References :

1.    Markowitz, S.D., Dawson, D.M., Willis, J., and Willson, K.V. (2002). Focus on colon cancer. Cancer Cell. 1, 233–236.

2.    Takeshita, S., Kikuno, R., Tezuka, K., and Amann, E. (1993). Osteoblastspecific factor 2: cloning of a putative bone adhesion protein with homology with the insect protein fasciclin I.Biochem. J. 294, 271–278.

3.    Nicholson, K.M., and Anderson, N.G. (2002). The protein kinase B/Akt signaling pathway in human malignancy. Cell. Signal. 14, 381–395.