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Mol. Cells 2013; 36(2): 177-184

Published online July 4, 2013

https://doi.org/10.1007/s10059-013-0061-6

© The Korean Society for Molecular and Cellular Biology

TrkC Promotes Survival and Growth of Leukemia Cells Through Akt-mTOR-Dependent Up-Regulation of PLK-1 and Twist-1

Min Soo Kim, Gyoung Mi Kim, Yun-Jeong Choi, Hye Joung Kim2, Yoo-Jin, Kim, and Wook Jin

1Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Korea, 2Department 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, 3Gachon Medical Research Institute, Gil Medical Center, Incheon 405-760, Korea, 4These authors contributed equally to this work.

Received: February 22, 2013; Revised: May 21, 2013; Accepted: June 10, 2013

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.

Keywords apoptosis, hematological malignancies, PI3K/Akt/Mtor, survival and growth, TrkC

Article

Research Article

Mol. Cells 2013; 36(2): 177-184

Published online August 31, 2013 https://doi.org/10.1007/s10059-013-0061-6

Copyright © The Korean Society for Molecular and Cellular Biology.

TrkC Promotes Survival and Growth of Leukemia Cells Through Akt-mTOR-Dependent Up-Regulation of PLK-1 and Twist-1

Min Soo Kim, Gyoung Mi Kim, Yun-Jeong Choi, Hye Joung Kim2, Yoo-Jin, Kim, and Wook Jin

1Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Korea, 2Department 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, 3Gachon Medical Research Institute, Gil Medical Center, Incheon 405-760, Korea, 4These authors contributed equally to this work.

Received: February 22, 2013; Revised: May 21, 2013; Accepted: June 10, 2013

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.

Keywords: apoptosis, hematological malignancies, PI3K/Akt/Mtor, survival and growth, TrkC

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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