Loss of SPHK1 fuels inflammation to drive KRAS-mutated lung adenocarcinoma

Inflammation is a widely recognized key contributor to KRAS-driven lung adenocarcinoma. Tumor associated macrophages are integral part of the tumor microenvironment, creating a supportive niche to sustain tumorigenesis. In the present study, we unravel a dichotomic role of sphingosine kinase 1 (SPHK1). We delineate SPHK1 as an oncogene, where its deletion markedly reduced proliferation of KRAS-mutated lung adenocarcinoma cells. However, in pre-clinical models, SPHK1 is a tumor suppressor, where its tumor intrinsic loss leads to disrupted lipid homeostasis, increased inflammation and hence augmented tumorigenesis. Overall design: Lung tumors were induced in KP and KPdSPHK1 mice 14 weeks prior of organ harvesting. Tissue was then frozen and RNA was from bulk lung tissue.