Ghrelin induces autophagy and CXCR4 expression via the SIRT1/AMPK axis in lymphoblastic leukemia cell lines |
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| Institution: | 1. Department of Microbiology and Immunology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran;2. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran;3. Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran;4. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran;5. Department of Epidemiology and Biostatistics, School of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran;6. Department of Pathology, Shahrekord University of Medical Sciences, Shahrekord, Iran;1. Department of Medical Physics, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran;2. Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran;1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao University, Qingdao, Shandong, 266071, China;2. Department of Nutrition, Texas A&M University, College Station, TX, 77843, United States;3. Department of Surgery, Valley Presbyterian Hospital, Van Nuys, CA, 91405, United States;4. Institute of Brain Sciences and Related Disorders, Qingdao University, Qingdao, Shandong, 266071, China;5. Department of Rehabilitation Medicine, Affiliated Hospital of Qingdao University, Qingdao, Shangdong, 266000, China;1. Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology [IMBICE, Argentine Research Council (CONICET) and Scientific Research Commission, Province of Buenos Aires (CIC-PBA), National University of La Plata], 1900 La Plata, Buenos Aires, Argentina;2. Laboratory of Experimental Neurodevelopment, Institute of Development and Pediatric Research (IDIP), La Plata Children’s Hospital and Scientific Research Commission, Province of Buenos Aires (CIC-PBA)], La Plata, Buenos Aires, Argentina |
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| Abstract: | T cell acute lymphoblastic leukemia (T-ALL) is one of the most frequent malignancies in children, and the CXCR4 receptor plays an important role in the metastasis of this malignancy. Ghrelin is a hormone with various functions including stimulation of the release of growth hormone and autophagy in cancer cells. Moreover, SIRT1 and AMPK (AMP-activated protein kinase) stimulate expression of proteins involved in autophagy. On the other hand, autophagic cell death can be an alternative target for cancer therapy, in the absence of apoptosis. The relationship between ghrelin and the SIRT1/AMPK axis and the resulting effects on autophagy, apoptosis, proliferation, and expression of CXCR4 and the ghrelin receptor (GHS-R1a), in Jurkat and Molt-4 human lymphoblastic cell lines was not previously clear. Here we demonstrate that SIRT1 expression is upregulated during the induction of autophagy by ghrelin, an effect that is inhibited by inactivation of SIRT1/AMPK axis. In addition, ghrelin can affect CXCR4 and GHS-R1a expression. In conclusion, this work reveals that ghrelin induces autophagy, invasion, and downregulation of ghrelin receptor expression via the SIRT1/AMPK axis in lymphoblastic cell lines. However, in these cell lines ghrelin-induced autophagy does not lead to cell death due to weak induction of apoptosis. |
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