Abstract
We show constitutive activation of Rho kinase (ROCK) in cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL, which is dependent on PI3K and Rho GTPase. Genetic or pharmacologic inhibition of ROCK in oncogene-bearing cells impaired their growth as well as the growth of acute myeloid leukemia patient-derived blasts and prolonged the life span of mice bearing myeloproliferative disease. Downstream from ROCK, rapid dephosphorylation or loss of expression of myosin light chain resulted in enhanced apoptosis, reduced growth, and loss of actin polymerization in oncogene-bearing cells leading to significantly prolonged life span of leukemic mice. In summary we describe a pathway involving PI3K/Rho/ROCK/MLC that may contribute to myeloproliferative disease and/or acute myeloid leukemia in humans.
Original language | English (US) |
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Pages (from-to) | 357-369 |
Number of pages | 13 |
Journal | Cancer cell |
Volume | 20 |
Issue number | 3 |
DOIs | |
State | Published - Sep 2011 |
Funding
We would like to thank Marilyn Wales for her administrative support. This work was supported in part by grants from National Institutes of Health (R01 HL077177 to R.K.; R01 HL08111 to R.K.; R01 HL075816 to R.K.; R01 CA134777 to R.J.C. and R.K.; and HL085098 to L.W.) and Riley Children's Foundation.
ASJC Scopus subject areas
- Oncology
- Cancer Research