ABSTRACT
Epithelial to mesenchymal transition (EMT) is a programme defined in epithelial cells and recognized as playing a critical role in cancer progression. Although melanoma is not a cancer of epithelial cells, hallmarks of EMT have been described to play a critical role in melanoma progression. Here, we demonstrate that long-term TGFß exposure can induce a dedifferentiated EMT-like state resembling a previously described invasive phenotype (EMT-like). TGFß-induced EMT-like is marked by the downregulation of melanocyte differentiation markers, such as MITF, and the upregulation of mesenchymal markers, such as N-cadherin, and an increase in melanoma cell migration and cell invasion. Pharmacological interference shows the dependency of TGFß-induced EMT-like on the activation of the PDGF signalling pathway and the subsequent activation of PI3K in human melanoma cells. Together, the data provide novel insights into the transcriptional plasticity of melanoma cells that might contribute to tumor progression in patients and propose avenues to therapeutic interventions.
Subject(s)
Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Melanoma/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism , Cell Differentiation , Cell Line, Tumor , Cell Movement , Disease Progression , Humans , Neovascularization, Pathologic , Phenotype , Platelet-Derived Growth Factor/metabolism , RNA, Small Interfering/metabolism , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
PURPOSE: To examine the impact of early-stage intense romantic love on sleep, daytime functioning and self-worth, adolescents in early-stage intense romantic love were compared to controls. In adolescence, falling in love is an important prerequisite for acquiring psychosocial and psychosexual skills. Early-stage intense romantic love involves physiological, cognitive, emotional, and behavioral dimensions: increased arousal, persistent thoughts for the beloved person, feelings of overwhelming joy, and efforts to sustain proximity to the person loved are prominent features of adolescents in a state of intense romantic love. The stage is comparable to a hypomanic-like state. However, no research has addressed this issue. Furthermore, no data are available with respect to sleep and sleep-related dimensions such as mood. METHOD: One hundred seven adolescents (mean age: 17.98 years +/- 1.33) took part in the study; 60 of them indicated they had recently fallen in love and experienced intense romantic love, 47 had a longer-lasting relationship or were singles. Following a screening interview for psychiatric disorders, participants completed questionnaires related to hypomania and sleep habits. Additionally, they completed a sleep log for seven consecutive nights. RESULTS: Compared to controls, adolescents in early-stage intense romantic love had increased scores on a hypomania scale, and recorded increased positive mood states in the mornings and in the evenings. These adolescents also recorded fewer hours of sleep with increased subjective sleep quality, lowered daytime sleepiness, and heightened concentration during the day. CONCLUSIONS: In adolescence, early-stage intense romantic love is comparable to a hypomanic state. This state is also reflected in altered sleep patterns, mood, and daytime functioning. Consequently, to not bias data in research with adolescents, current stage of love should be taken into account.
