Secondly, FBXL2 inhibits cell proliferation in H292, PC9 or H1975 cells, all of which bear wild-type Ras alleles, while it exhibits little effects on A549 or H1299 cells harboring activated Ras, an essential downstream effector of EGFR, in keeping with the clinical guideline that EGFR-TKI-based treatment of NSCLC is not applicable to patients with activated Ras44,45. Here, FBXL2 is linked to non-small cell lung carcinoma.