Non-small cell lung cancer (NSCLC), the most common lung cancer, is also the most lethal cancer worldwide. The protein CPNE1 has been found to promote NSCLC, but it’s not clear how. To find out, researchers recently manipulated CPNE1 expression in NSCLC cells in vitro. CPNE1 overexpression activated cancer progression processes, such as proliferation, migration, invasion, and MET signaling, while CPNE1 silencing produced the opposite effects. Silencing RACK1, another cancer-driving protein, suppressed the tumor formation and MET signaling activation caused by CPNE1 overexpression, confirming that RACK1 mediates CPNE1-induced cancer progression and suggesting that MET is involved. Since CPNE1 is also believed to activate EGFR signaling, the researchers tested the effects of both MET and EGFR inhibition on NSCLC tumors in mice. Combined treatment with both the MET inhibitor JNJ-38877605 and the EGFR inhibitor gefitinib inhibited tumor growth better than either treatment alone and reduced the activation of downstream signaling pathways. Although the exact mechanisms need further study, the results reveal that CPNE1 drives NSCLC via the MET pathway by interacting with RACK1 and suggest that dual inhibition of MET and EGFR is a promising strategy for NSCLC treatment.