PAK1 and ILK Form a Vicious Oncogenic Cycle.

Both PAK１ and ILK are oncogenic kinases, and anti-PAK１ and anti-ILK drugs share a very unique property in common, inhibiting　the　growth　of　cancers selectively　without　affecting　normal　cell　growth.　　These　findings　suggest　the　possibility that these two kinases are closely linked.

Around 2007 Rakesh Kumar`s group at MD Anderson Cancer Center in Texas found the first link. PAK1 directly phosphorylates and activates ILK (1). In 2011 Dai Chung`s group at Vanderbilt University revealed another link. ILK down-regulates the tumor suppressive phosphatase PTEN, thereby activating both AKT and PAK1 (2).

In other words PAK1 and ILK form a vicious oncogenic cycle, just like PAK1 and estrogen receptor (ER). Consequently, ILK and ER would also form a third vicious oncogenic cycle via PAK1.


References:

1. Acconcia, F. et al. Phosphorylation-dependent regulation of nuclear localization and functions of integrin-linked kinase. Proc Natl Acad Sci U S A. 2007 ;104:6782-7.

2. Taylor, C. et al. Integrin-linked kinase regulates phosphatase and tensin homologue activity to promote tumorigenesis in neuroblastoma cells. Surgery. 2011 , in press.