Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway.
Molecular mechanisms associated with tumor metastasis remain poorly understood. Here we report that acquired expression of periostin by colon cancer cells greatly promoted metastatic development of colon tumors. Periostin is overexpressed in more than 80% of human colon cancers examined with highest expression in metastatic tumors. Periostin expression dramatically enhanced metastatic growth of colon cancer by both preventing stress-induced apoptosis in the cancer cells and augmenting endothelial cell survival to promote angiogenesis. At the molecular level, periostin activated the Akt/PKB signaling pathway through the alpha(v)beta(3) integrins to increase cellular survival. These data demonstrated that the survival-promoting function is crucial for periostin to promote tumor metastasis of colon cancer.
Bao
Shideng
S
The Key Laboratory for Cell Biology and Tumor Cell Engineering, The Ministry of Education of China, The School of Life Sciences, Xiamen University, Fujian 361005, China.
Ouyang
Gaoliang
G
Bai
Xuefang
X
Huang
Zhi
Z
Ma
Chaoyu
C
Liu
Ming
M
Shao
Rong
R
Anderson
Ryan M
RM
Rich
Jeremy N
JN
Wang
Xiao-Fan
XF
D000818:Animals; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D015687:Cell Hypoxia; D002470:Cell Survival; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; C512835:POSTN protein, human; C082838:Postn protein, mouse; D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt