Abstract:
:Tumor-associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF-1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF-1-induced macrophage migration. Disruption of Akt2 expression by small interference RNA impaired chemotaxis of both THP-1 cells and mouse peritoneal macrophages. Phosphorylation of PKCzeta, an essential component in chemotaxis signaling pathway, was reduced. LIMK/Cofilin, downstream of PKCzeta, regulated cytoskeleton rearrangement during cell migration. Disruption of Akt2 expression inhibited CSF-1-induced LIMK/Cofilin phosphorylation, which contributed to defects in actin polymerization and chemotaxis. Furthermore, MCP-1, a chemokine, -induced macrophage chemotaxis was also impaired. Taken together, our results demonstrated that Akt2 plays an essential role in both CSF-1- and chemokine-induced chemotaxis of macrophages.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Zhang B,Ma Y,Guo H,Sun B,Niu R,Ying G,Zhang Ndoi
10.1002/eji.200838809subject
Has Abstractpub_date
2009-03-01 00:00:00pages
894-901issue
3eissn
0014-2980issn
1521-4141journal_volume
39pub_type
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