We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
ILK mediates actin filament rearrangements and cell migration and invasion through PI3K/Akt/Rac1 signaling.
- Authors
Yong Qian; Xiaosong Zhong; Flynn, Daniel C.; Zheng, Jenny Z.; Meng Qiao; Chuanyue Wu; Shoukat Dedhar; Xianglin Shi; Bing-Hua Jiang
- Abstract
One of the hallmarks of integrin signaling is an increase in cell migration and invasion, both of which are associated with actin filament rearrangements. Integrin-linked kinase (ILK) is a cytoplasmic effector of integrin receptors. ILK is known to be involved in multiple cellular functions. However, the signaling pathways involved in ILK-mediated cellular structure and motility remain to be elucidated. Here, we have demonstrated that overexpression of ILK was sufficient to induce actin filament rearrangements, to form cell motility structures, and to increase cell migration and invasion in a phosphatidylinositol 3-kinase (PI3K)-dependent manner. This corresponds with the activation of both Akt and p70 ribosomal protein S6 kinase (p70S6K1). Overexpression of dominant-negative mutants of Akt inhibited ILK-dependent activation of p70S6K1, indicating that Akt is upstream of p70S6K1 in response to ILK signaling. Overexpression of ILK was sufficient to induce Rac1 activation, which was abolish by a PI3K inhibitor, indicating that Rac1 activity is involved in ILK signaling in a PI3K dependent manner. Inhibition of Akt, Rac1, or p70S6K1 inhibited the effects of ILK on actin filaments and cell migration, suggesting a regulatory role of the PI3K/Akt/p70S6K1/Rac1 signaling pathway in response to ILK signaling. We have shown that overexpression of a dominant-negative ILK was sufficient to abolish fibronectin peptide (PHSRN)-induced rearrangements of actin filaments and cell migration and invasion. Taken together, our results identify a mechanism through which ILK can regulate both integrin-associated rearrangements of actin filaments and cell migration and invasion at the integrin receptor-proximal region.Oncogene (2005) 24, 3154-3165. doi:10.1038/sj.onc.1208525 Published online 21 February 2005
- Subjects
CELL migration; CYTOLOGY; PROTEINS; ACTOMYOSIN; FIBRONECTINS; BLOOD proteins
- Publication
Oncogene, 2005, Vol 24, Issue 19, p3154
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208525