Recently, we have published that sphingosine-1-phosphate (S1P), produced by sphingosine kinase 1 (SphK1) in breast cancer, signals through S1P receptor 1 (S1PR1) and activates the amplification loop of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) in obesity-related inflammation, which promotes lung metastasis and worsens survival as well as increases resistance to therapy [4–6]. The gene discussed is TNF; the disease is obesity due to melanocortin 4 receptor deficiency.