Small molecule inhibition of cytoskeletal dynamics in melanoma tumors results in altered transcriptional expression patterns of key genes involved in tumor initiation and progression.

BACKGROUND

Rho kinase signaling plays an important role in the oncogenic process largely through its regulation of F-actin dynamics, and inhibition of this pathway results in reduction in tumor volume and metastasis across a number of tumor types. While the cytoskeletal-regulatory role of Rho kinase has been a topic of in-depth study, the mechanisms linking Rho kinase to altered gene expression are largely unknown.

MATERIALS AND METHODS

Global gene expression analysis was performed on melanoma tumors treated with sham or the small molecule inhibitor Y27632.

RESULTS

Inhibition of Rho kinase activity in melanoma tumors results in a statistically significant change in gene transcription of 94 genes, many of which are critically involved in tumor initiation and progression.

CONCLUSION

In addition to regulating tumorigenesis through modulation of the phosphoproteome, Rho kinase signaling also contributes to the regulation of the tumor transcriptome.