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 |
|---|---|
| Pages (from-to) | 357-369 |
| Number of pages | 13 |
| Journal | Cancer Cell |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2011 |
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ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Oncology
Cite this
Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL. / Mali, Raghuveer Singh; Ramdas, Baskar; Ma, Peilin; Shi, Jianjian; Munugalavadla, Veerendra; Sims, Emily; Wei, Lei; Vemula, Sasidhar; Nabinger, Sarah C.; Goodwin, Charles B.; Chan, Rebecca; Traina, Fabiola; Visconte, Valeria; Tiu, Ramon V.; Lewis, Timothy A.; Stern, Andrew M.; Wen, Qiang; Crispino, John D.; Boswell, H.; Kapur, Reuben.
In: Cancer Cell, Vol. 20, No. 3, 09.2011, p. 357-369.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL
AU - Mali, Raghuveer Singh
AU - Ramdas, Baskar
AU - Ma, Peilin
AU - Shi, Jianjian
AU - Munugalavadla, Veerendra
AU - Sims, Emily
AU - Wei, Lei
AU - Vemula, Sasidhar
AU - Nabinger, Sarah C.
AU - Goodwin, Charles B.
AU - Chan, Rebecca
AU - Traina, Fabiola
AU - Visconte, Valeria
AU - Tiu, Ramon V.
AU - Lewis, Timothy A.
AU - Stern, Andrew M.
AU - Wen, Qiang
AU - Crispino, John D.
AU - Boswell, H.
AU - Kapur, Reuben
PY - 2011/9
Y1 - 2011/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052576659&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052576659&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2011.07.016
DO - 10.1016/j.ccr.2011.07.016
M3 - Article
C2 - 21907926
AN - SCOPUS:80052576659
VL - 20
SP - 357
EP - 369
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 3
ER -