Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8
Author
Li, Zhigang; Dong, Lixue; Dean, Eric; Yang, Li V.
Abstract
Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression.
Subject
Date
2013-10
Citation:
APA:
Li, Zhigang, & Dong, Lixue, & Dean, Eric, & Yang, Li V.. (October 2013).
Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8.
International Journal of Molecular Sciences,
14(10),
20236-
20255. Retrieved from
http://hdl.handle.net/10342/5738
MLA:
Li, Zhigang, and Dong, Lixue, and Dean, Eric, and Yang, Li V..
"Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8". International Journal of Molecular Sciences.
14:10. (20236-20255),
October 2013.
September 26, 2023.
http://hdl.handle.net/10342/5738.
Chicago:
Li, Zhigang and Dong, Lixue and Dean, Eric and Yang, Li V.,
"Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8," International Journal of Molecular Sciences 14, no.
10 (October 2013),
http://hdl.handle.net/10342/5738 (accessed
September 26, 2023).
AMA:
Li, Zhigang, Dong, Lixue, Dean, Eric, Yang, Li V..
Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8. International Journal of Molecular Sciences.
October 2013;
14(10):
20236-20255.
http://hdl.handle.net/10342/5738. Accessed
September 26, 2023.
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