Melanoma progression and resistance to therapy are associated with faulty regulation of signalling molecules including the central transcription factor NF-κB. Increased expression of the c-Rel subunit of NF-κB has been described in progressing melanoma, though mechanistic implications of this upregulation remain unclear. To elucidate the functional role of c-Rel in melanoma biology, we have assessed its expression in human melanoma as well as in melanoma cell lines. Suppression of c-Rel expression in four melanoma cell lines resulted in reduced growth and altered cell cycle regulation, namely G2/M and polyploid phase induction. Moreover, mitotic spindle morphology was profoundly altered in three of the cell lines with a predominance of monopolar structures. These findings suggest that c-Rel is involved in G2/M phase regulation, prevention of polyploidy and, consequently, chromosomal stability. Our results highlight a novel tumor-promoting function of c-Rel in human melanoma cells through governing cell cycle regulation.
Keywords: NF-κB; c-Rel; cell cycle; melanoma; mitotic spindle.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.