Smoking
carcinogen nicotine-derived
nitrosamine ketone (NNK) is the most potent contributor to
lung adenocarcinoma (LUAD) development, but the mechanism has not been fully elucidated. Here, we reported that
fatty acid translocase CD36 was significantly overexpressed in both human LUAD tissues and NNK-induced A/J mice LUAD
tumors. The overexpressed CD36 was positively correlated with
Src kinase activation, smoking status,
metastasis, and worse overall survival of patients with smoking history. Upon NNK binding with α7
nicotinic acetylcholine receptor (α7nAChR), sarcolemmal CD36 was increased and it interacted with surface α7nAChR and cytosol Src simultaneously, which in turn activated Src and downstream pro-carcinogenic
kinase ERK1/2 and Akt, and finally caused LUAD cells to form subcutaneous and pulmonary metastatic
tumors. This process could be blocked by CD36 knockdown and CD36 irreversible inhibitor SSO. Furthermore, the effect of NNK was inhibited obviously in CD36-/- A/J mice. Thus, targeting CD36 may provide a breakthrough
therapy of LUAD.