Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL

Raghuveer Singh Mali, Baskar Ramdas, Peilin Ma, Jianjian Shi, Veerendra Munugalavadla, Emily Sims, Lei Wei, Sasidhar Vemula, Sarah C. Nabinger, Charles B. Goodwin, Rebecca J. Chan, Fabiola Traina, Valeria Visconte, Ramon V. Tiu, Timothy A. Lewis, Andrew M. Stern, Qiang Wen, John D. Crispino, H. Scott Boswell, Reuben Kapur

Research output: Contribution to journalArticle

59 Scopus citations

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 languageEnglish (US)
Pages (from-to)357-369
Number of pages13
JournalCancer Cell
Volume20
Issue number3
DOIs
StatePublished - Sep 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Mali, R. S., Ramdas, B., Ma, P., Shi, J., Munugalavadla, V., Sims, E., Wei, L., Vemula, S., Nabinger, S. C., Goodwin, C. B., Chan, R. J., Traina, F., Visconte, V., Tiu, R. V., Lewis, T. A., Stern, A. M., Wen, Q., Crispino, J. D., Boswell, H. S., & Kapur, R. (2011). Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL. Cancer Cell, 20(3), 357-369. https://doi.org/10.1016/j.ccr.2011.07.016