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.

KEYWORDS:

• Cdc42
• PI3K
• Rho GTPases
• melanoma

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was supported by the Central Michigan University, Michigan State University, College Of Human Medicine, and Ferris State University.