TIS21 inhibits cell migration and invasion

TIS21/BTG2/PC3 is tumor suppressor gene and frequently downregulated in cancer tissue. In human tissue, decreased BTG2 is correlated with cancer cell metastasis, suggesting that suppression of BTG2 has a critical role in cancer cell migration and invasion. When we overexpressed TIS21 in A549 cells, cell migration and invasion were dramatically inhibited. Furthermore, cell morphology was changed like round shape. TIS21 overexpression was correlated with downregulation of focal adhesion kinase (FAK) tyr576 and tyr925 residues phosphorylation. However, tyr397 which was autophosphorylation site was not influenced by TIS21 expression. c-Src phosphorylation which was upstream of FAK was not influenced by TIS21, however, c-Src kinase activity was significantly decreased by TIS21. When we measured Src oxidized state in the cells, TIS21 increased Src reduction state and TIS21 inhibited ROS generation by localization in the mitochondria. Furthermore, TIS21 inhibited FoxM1 phosphorylation and downregulated MMP-2 expression. In conclusion, TIS21 inhibited cell migration and invasion by inhibition of Src by downregulation of ROS generation in mitochondria, furthermore, TIS21 inhibited FoxM1 phosphorylation and decreased MMP-2 expression. AKT interacted with TIS21 and phosphorylated TIS21 at Ser31 in vitro. Phosphorylated TIS21 by AKT led to the loss of its inhibitory effects on cells migration and invasion. Furthermore, AKT mediated phosphorylation of TIS21 also abrogated its inhibitory effects on FAK phosphorylation as well as MMP-2 mRNA downregulation.

Author dc:creator

• 임, 서경

Contributors dc:contributor

• 박, 태준
• 대학원 의생명과학과
• 200824176

• AKT
• TIS21/BTG2/PC3
• FAK
• Src
• MMP-2
• ROS
• FoxM1
• Mitochondria

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000011875
000000011875

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/4412