Clear-cell renal cell carcinoma (ccRCC), a tubular epithelial malignancy, secretes tumor necrosis factor (TNF), which signals ccRCC cells in an autocrine manner via two cell surface receptors, TNFR1 and TNFR2, to activate shared and distinct signaling pathways. The gene discussed is TNFRSF1A; the disease is clear cell renal carcinoma.