Soluble Guanylate Cyclase β1 Subunit Represses Human Glioblastoma Growth

Authors

Haijie Xiao, Department of Biochemistry and Molecular Medicine, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA.
Haifeng Zhu, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), The University of Texas Health Science Center at Houston, 7000 Fannin Street, Houston, TX 77030, USA.
Oliver Bögler, Brain Tumor Center, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Fabiola Zakia Mónica, Department of Biochemistry and Molecular Medicine, The George Washington University, 2300 I Street NW, Washington, DC 20037, USA.
Alexander Y. Kots, Veteran Affairs Palo Alto Health Care System, Department of Veteran Affairs, Palo Alto, CA 94304, USA.
Ferid Murad, Veteran Affairs Palo Alto Health Care System, Department of Veteran Affairs, Palo Alto, CA 94304, USA.
Ka Bian, Veteran Affairs Palo Alto Health Care System, Department of Veteran Affairs, Palo Alto, CA 94304, USA.

Document Type

Journal Article

Publication Date

3-2-2023

Journal

Cancers

Volume

15

Issue

5

DOI

10.3390/cancers15051567

Keywords

CDK6; G0 arrest; glioblastoma; integrin α6; nucleus; p53; sGCβ1

Abstract

Malignant glioma is the most common and deadly brain tumor. A marked reduction in the levels of sGC (soluble guanylyl cyclase) transcript in the human glioma specimens has been revealed in our previous studies. In the present study, restoring the expression of sGCβ1 alone repressed the aggressive course of glioma. The antitumor effect of sGCβ1 was not associated with enzymatic activity of sGC since overexpression of sGCβ1 alone did not influence the level of cyclic GMP. Additionally, sGCβ1-induced inhibition of the growth of glioma cells was not influenced by treatment with sGC stimulators or inhibitors. The present study is the first to reveal that sGCβ1 migrated into the nucleus and interacted with the promoter of the gene. Transcriptional responses induced by sGCβ1 caused the G0 cell cycle arrest of glioblastoma cells and inhibition of tumor aggressiveness. sGCβ1 overexpression impacted signaling in glioblastoma multiforme, including the promotion of nuclear accumulation of p53, a marked reduction in CDK6, and a significant decrease in integrin α6. These anticancer targets of sGCβ1 may represent clinically important regulatory pathways that contribute to the development of a therapeutic strategy for cancer treatment.

APA Citation

Xiao, Haijie; Zhu, Haifeng; Bögler, Oliver; Mónica, Fabiola Zakia; Kots, Alexander Y.; Murad, Ferid; and Bian, Ka, "Soluble Guanylate Cyclase β1 Subunit Represses Human Glioblastoma Growth" (2023). GW Authored Works. Paper 2622.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2622

Department

Biochemistry and Molecular Medicine