CDC42 Regulates Cell Proliferation and Apoptosis in Bladder Cancer via the IQGAP3-Mediated Ras/ERK Pathway.

Abstract

Bladder cancer (BC) is the most common malignant tumour of the urinary system. The current conventional treatments for BC have certain limitations. It is very urgent and necessary to find new treatment strategies for BC. Our study elucidated the underlying regulatory mechanisms of cell division control protein 42 homologue (CDC42) to regulate the development of BC. Quantitative real-time polymerase chain reaction, Western blot, immunofluorescence and immunohistochemistry were used to assess the expression of CDC42 and IQ motif-containing GTPase-activating protein 3 (IQGAP3) in BC tissues and BC cells. We induced the knockdown or overexpression by transfecting sh-CDC42 or oe-IQGAP3 into BC cells. In addition, cell proliferation and apoptosis were evaluated by cell counting kit-8 and flow cytometry assays, respectively. Moreover, proteins involved in the rat sarcoma (Ras)/extracellular regulated protein kinase (ERK) pathway were determined by Western blot. The expression of CDC42 and IQGAP3 was markedly upregulated in both BC tissues and BC cells. CDC42 silencing downregulated the expression of IQGAP3 and suppressed the Ras/ERK pathway. In addition, CDC42 silencing markedly promoted apoptosis and inhibited proliferation in BC cells. Further experiments showed that overexpression of IQGAP3 dramatically abolished the bioeffects mediated by CDC42 silencing on the proliferation and apoptosis of BC cells. All our results suggested that CDC42 promoted the Ras/ERK pathway by regulating IQGAP3, thus enhancing cell proliferation and suppressing cell apoptosis in BC cells and ultimately participating in the pathogenesis of BC.

• Authors: Gang Li, Yu Wang, Xiao-Bo Guo, Bo Zhao
• Journal: Biochemical genetics (Biochem Genet) Vol. 60 Issue 6 Pg. 2383-2398 (Dec 2022) ISSN: 1573-4927 [Electronic] United States
• PMID: 35412170 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• GTPase-Activating Proteins
• IQGAP3 protein, human
• Protein Kinases
• CDC42 protein, human
• cdc42 GTP-Binding Protein

Topics

• Humans
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• GTPase-Activating Proteins (genetics, metabolism)
• MAP Kinase Signaling System
• Protein Kinases
• Urinary Bladder Neoplasms (genetics)
• cdc42 GTP-Binding Protein (genetics, metabolism)