As a main upstream in MAPK signaling transduction, MAPK kinase kinase 8 (MAP3K8), which is also known as tumor progression locus 2 (Tpl2), can activate a plethora of downstream molecules including MEK, ERK, and JNK to influence the growth and survival of cancer cells in concert with other signaling pathways, such as nuclear factor kappa-B (NFKB), tumor necrosis factor (TNF), and interleukin-1 (IL-1) (Lee et al., 2015a; Braicu et al., 2019). The gene discussed is TNF; the disease is cancer.