Overexpression of SLC25A15 is involved in the proliferation of cutaneous melanoma and leads to poor prognosis.

Melanoma is a skin tumor with a high degree of malignancy, poor prognosis and few effective therapies. Deprivation of the arginine from cancer cells through transport inhibition and arginine depletion is a novel strategy for cancer therapy. In this study, we have investigated the effect of SLC25A15, which encodes the mitochondrial ornithine carrier 1, on melanoma progression. Using bioinformatics methods to screen the data from TCGA and GEO, we found that SLC25A15 is overexpressed in patients with melanoma and negatively related with the overall and disease-free survival rates. Knockdown the expression of SLC25A15 by siRNA could effectively inhibit the proliferation of A375 melanoma cells, as detected by CCK8 and colony formation. Furthermore, SLC25A15 siRNA was able to promote apoptosis of A375 cells, which exhibited decreased expression levels of the anti-apoptotic protein Bcl-2 while showing increased pro-apoptotic protein Bax and cleaved caspase-3. All these results suggest that the overexpression of SLC25A15 is involved in the progression of melanoma and may predict the prognosis of melanoma. This may shed new lights on the diagnosis and therapy of melanoma in the future.

Social defeat stress promotes tumor growth and angiogenesis by upregulating vascular endothelial growth factor/extracellular signal-regulated kinase/matrix metalloproteinase signaling in a mouse model of lung carcinoma.

Numerous epidemiological and experimental animal studies have indicated that chronic psychological stress may promote tumor development. However, the underlying molecular mechanisms by which chronic stress promotes tumorigenesis remain to be fully elucidated and animal models have not yet been well established. In the present study, an established mouse model of repeated social defeat stress (RSDS), was generated and used to investigate the effect of stress on tumor growth and metastasis. C57BL/6 mice were exposed to RSDS for 10 days, followed by subcutaneousl inoculation with Lewis lung carcinoma cells for seven days. The tumor weight and volume as well as the number of the lung metastatic nodules were then determined. Vascular endothelial growth factor (VEGF) serum levels were measured using ELISAs. In addition, expression levels of VEGF receptor (VEGFR) and L1 cell adhesion molecule (L1CAM) messenger (m)RNA were confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, protein expression levels of phosphorlyated extracellular signal-regulated kinase (pERK), matrix metalloproteinase (MMP)-2 and MMP-9 were examined using western blot analysis. The results showed that RSDS significantly increased the weight and the volume of the primary tumor as well as the number of the lung metastatic nodules. Serum VEGF levels were significantly higher in the tumor-stress group compared with those of the unstressed tumor mice. In addition, tumors in stressed animals demonstrated markedly enhanced expression of VEGFR-2 and L1CAM mRNA as well as pERK, MMP-2 and MMP-9 protein expression. In conclusion, these results suggested that RSDS contributed to lung cancer progression, angiogenesis and metastasis, which was partially associated with increased VEGF secretion and therefore the activation of the ERK signaling pathway, resulting in the induction of MMP-2 and MMP-9 protein expression.