We recently demonstrated a correlation of cofilin-1 levels, a key protein for tumor invasion, with different histopathological parameters associated with melanoma malignancy as well as a negative correlation with survival.
These studies demonstrate that host p18 imposes the requirement for the viral cyclin to reactivate from latency by functioning in latently infected cells and that p18 expression is associated with decreased disease, thereby identifying p18 as a compelling host target to limit chronic gammaherpesvirus pathogenesis.<b>IMPORTANCE</b> Gammaherpesviruses are ubiquitous viruses associated with multiple malignancies.
Profilin 1, cofilin 1, and vasodialator-stimulated phosphoprotein (VASP) are actin-binding proteins (ABP) that regulate actin remodeling and facilitate cancer cell metastases. miR-17-92 is highly expressed in metastatic tumors and profilin1 and cofilin1 are predicted targets.
To determine the molecular basis for the inhibitory function of p18, we introduced 11 missense mutations of conserved residues that were identified in p16 of cancer cell lines into p18.
The questions arise if high level p18 expression in certain malignancies may play a primary role in driving cell proliferation or, based on chromosomal localization and inactivation of p18 expression in one lymphoma, if p18 may act as a tumor suppressor.