SummaryDeviating from the normal karyotype dramatically changes gene dosage, in turn decreasing the robustness of biological networks. Consequently, aneuploidy is poorly tolerated by normal somatic cells and acts as a barrier to transformation. Paradoxically, however, karyotype heterogeneity drives tumor evolution and the emergence of therapeutic drug resistance. To better understand how cancer cells tolerate aneuploidy, we focused on the p38 stress response kinase. We show here that p38-deficient cells upregulate glycolysis and avoid post-mitotic apoptosis, leading to the emergence of aneuploid subclones. We also show that p38 deficiency upregulates the hypoxia-inducible transcription factor Hif-1α and that inhibiting Hif-1α restores apoptosis in p38-deficent cells. Because hypoxia and aneuploidy are both barriers to tumor progression, the ability of Hif-1α to promote cell survival following chromosome missegregation raises the possibility that aneuploidy tolerance coevolves with adaptation to hypoxia.

The oestrogen-dependent regulation of cell behaviour is realised by stimulation of specific oestrogen receptors. The classical oestrogen receptors ERα and ERβ are transcription factors, and they modulate expression of hormonally regulated genes, while the third one, GPER, is thought to be responsible for the observed rapid, non-genomic cellular response. Oestrogen dependency is attributed to a number of cancers, including breast, ovarian and endometrial cancer; however, there is still growing evidence that melanoma should also be cited as a hormonally dependent tumour. This comes from the observations of gender-related differences in melanoma progression and reports concerning the history of the malignant course of melanomas during pregnancy. Although, the observations of oestrogen regulation of melanoma progression are controversial, the effect of oestrogen should not be neglected, as the skin possesses its own hormonal microenvironment. This aspect of melanoma progression should be taken under careful consideration as it may offer new therapeutic possibilities.

BE£KOT K., BUBKA M., LITYÑSKA A. 2016. Expression of caveolin-1 in human cutaneous and uveal melanoma cells. Folia Biologica (Kraków) 64: 145-151.Caveolin-1 can act as a tumour promoter or suppressor depending on the cancer type and stage. In melanoma, information available concerning its expression is ambiguous. In this study, we investigated caveolin-1 mRNA and protein expression levels in human melanoma cell lines of different origin and progression stages. Metastatic cutaneous (WM-266-4, A375), primary cutaneous (WM-115, IGR-39) and primary uveal (mel-202, 92-1) cells were used for quantitative RT-PCR, Western blotting and confocal microscopy. We observed significantly higher expression of caveolin-1 mRNA in cutaneous than in uveal melanoma cells. In accordance, immunostaining of caveolin-1 was stronger in cutaneous cell extracts, while protein bands of uveal origin displayed weak signals. Finally, we detected differences in the caveolin-1 subcellular pattern of distribution between primary and metastatic cells. Overall, this is the first demonstration of caveolin-1 expression in human primary uveal melanoma cell lines and observation that the origin of cells (uveal/cutaneous) has an impact when considering the utility of caveolin-1 as a melanoma cell marker.