Agradecimentos: The authors sincerely thank the support of Raymond Sawaya of the Department of Neurosurgery and Brain Tumor Center, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; Kazufumi Ohshiro, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Department of Medicine, Northwell Health, Manhasset, New York; Zheng Fang, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), The University of Texas Health Science Center at Houston, Texas; and Jun Liu, Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, District of Columbia. Fabiola Zakia Mónica acknowledges FAPESP (2013/02246-7), CAPES (BEX 6718/14-0), and UNICAMP for research support. This study was partially supported by the National Institute of General Medical Sciences, National Institutes of Health (grant GM-076695-02), the Department of Defense (grant T5-0004271), and a Merit Review Award no. 1 I01 BX005709-01 from the Biomedical Laboratory Research & Development Service, the United States Department of Veteran Affairs. The content of this publication does not represent the views of the U.S. Department of Veterans Affairs of the United States Government Ver menos

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 sGCß1 alone repressed the aggressive course of glioma. The antitumor effect of sGCß1 was not associated with enzymatic activity of sGC since overexpression of sGCß1 alone did not influence the level of cyclic GMP. Additionally, sGCß1-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 sGCß1 migrated into the nucleus and interacted with the promoter of the TP53 gene. Transcriptional responses induced by sGCß1 caused the G0 cell cycle arrest of glioblastoma cells and inhibition of tumor aggressiveness. sGCß1 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 a6. These anticancer targets of sGCß1 may represent clinically important regulatory pathways that contribute to the development of a therapeutic strategy for cancer treatment Ver menos