PI3K Functions Downstream of Cdc42 to Drive Cancer phenotypes in a Melanoma Cell Line.

Abstract

Rho proteins are part of the Ras superfamily, which function to modulate cytoskeletal dynamics including cell adhesion and motility. Recently, an activating mutation in Cdc42, a Rho family GTPase, was found in a patient sample of melanoma. Previously, our work had shown the PI3K was important downstream of mutationally active Cdc42. Our present study sought to determine whether PI3K was a crucial downstream partner for Cdc42 in a melanoma cells line with a BRAF mutation, which is the most common mutation in cutaneous melanoma. In this work we were able to show that Cdc42 contributes to proliferation, anchorage-independent growth, cell motility and invasion. Treatment with a pan-PI3K inhibitor was able to effectively ameliorate all these cancer phenotypes. These data suggest that PI3K may be an important target downstream of Cdc42 in melanoma.

• Authors: Rosemary Poku, Felix Amissah, Jamie K Alan
• Journal: Small GTPases (Small GTPases) Vol. 14 Issue 1 Pg. 1-13 (12 2023) ISSN: 2154-1256 [Electronic] United States
• PMID: 37114375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphatidylinositol 3-Kinases
• cdc42 GTP-Binding Protein
• rho GTP-Binding Proteins

Topics

• Humans
• Melanoma (genetics, metabolism)
• Phosphatidylinositol 3-Kinases
• Skin Neoplasms
• cdc42 GTP-Binding Protein (genetics, metabolism)
• rho GTP-Binding Proteins (metabolism)
• Cell Line
• Phenotype