The cell cycle–related genes AURORA A and Forkhead box M1 (FOXM1) are overexpressed in melanoma. AURKA overexpression was associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAFV600E mutation. Activated MAPK-ERK signalling pathway mediates robust AURKA promoter activation, thereby knockdown of BRAFV600E and ERK inhibition results in reduced AURKA transcription and expression.
The knockdown of BRAFV600E also reduces the expression of FOXM1 in BRAFV600E cells. Moreover, AURORA A and FOXM1 inhibition by either genetic knockdown or pharmacologic inhibitors impair melanoma growth and survival both in culture and in vivo, underscoring their therapeutic value for melanoma patients who fail to benefit from BRAF/MEK inhibition.
http://www.jidonline.org/article/S0022-202X(17)30115-X/fulltext
