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TrkC promotes survival and growth of leukemia cells through Akt-mTOR-Dependent Up-Regulation of PLK-1 and Twist-1

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Molecules and Cells

Abstract

It has been suggested that activation of receptor PTKs is important for leukemogenesis and leukemia cell response to targeted therapy in hematological malignancies including leukemia. PTKs induce activation of the PI3K/Akt/mTOR pathway, which can result in prevention of apoptosis. Here, we describe an important role of the TrkC-associated molecular network in the process of leukemogenesis. TrkC was found to be frequently overexpressed in human leukemia cells and leukemia subtypes. In U937 human leukemia cells, blockade of TrkC using small hairpin RNA (shRNA) specific to TrkC or K562a, a specific inhibitor of TrkC, resulted in a significant decrease in growth and survival of the cells, which was closely associated with reduced mTOR level and Akt activity. In addition, TrkC enhances the survival and proliferation of leukemia, which is correlated with activation of the PI3K/Akt pathway. Moreover, TrkC significantly inhibits apoptosis via induction of the expression of PLK-1 and Twist-1 through activation of AKT/mTor pathway; therefore, it plays a key role in leukemogenesis. These findings reveal an unexpected physiological role for TrkC in the pathogenesis of leukemia and have important implications for understanding various hematological malignancies.

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Authors and Affiliations

  1. Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, 406-840, Korea

    Min Soo Kim, Gyoung Mi Kim, Yun-Jeong Choi & Wook Jin

  2. Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea

    Hye Joung Kim & Yoo-Jin Kim

  3. Gachon Medical Research Institute, Gil Medical Center, Incheon, 405-760, Korea

    Wook Jin

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  1. Min Soo Kim
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  2. Gyoung Mi Kim
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  3. Yun-Jeong Choi
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  4. Hye Joung Kim
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  5. Yoo-Jin Kim
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Correspondence to Yoo-Jin Kim or Wook Jin.

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These authors contributed equally to this work.

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Kim, M.S., Kim, G.M., Choi, YJ. et al. TrkC promotes survival and growth of leukemia cells through Akt-mTOR-Dependent Up-Regulation of PLK-1 and Twist-1. Mol Cells 36, 177–184 (2013). https://doi.org/10.1007/s10059-013-0061-6

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