Fig. 1.

Expression of intracellular markers, SAE2 and ATAD3A, affect sensitivity of EGFR-mutated lung adenocarcinoma (LADC) cells to tyrosine kinase inhibitors, gefitinib or erlotinib. a LADC cells, carrying mutated EGFR (H1975), expressed abundant ATAD3A, an anti-apoptotic factor [9], as determined by a Western blotting analysis. b ATAD3A protein was highly expressed in EGFR-mutated H1975 (the left panel) and, intermediately, in the wild-type A549 (the right panel) cells. Some of the EGFR-mutated H1975 cells were elongated, scattered, and crescent shape (dark arrows), resembling phenotypes of mesenchymal cells [21], implicating that mutated EGFR could be associated with epithelial-to-mesenchymal transition (EMT) of LADC cells. c Knockdown of SAE2 expression (SAE2 ) increased ATAD3A expression. d In SAE2^KD cells, gefitinib sensitivity was also increased, suggesting that SAE2 could be an intracellular sensor of gefitinib. It is therefore worth noting that gefitinib sensitivity of SAE2^KD A549 cells was equivalent to that of H1975 cells (ID50 ~ 25 μM). e Silencing of SAE2 expression increased erlotinib sensitivity of A549 cells as well. However, SAE2^KD A549 cells (ID ~ 50 μM) were more resistant than H1975 cells (ID ~ 5.6 μM) to erlotinib. f Silencing of ATAD3A (ATAD3A ) reduced expression of EGFR and AIF. g Increase of gefitinib sensitivity was thus anticipated in ATAD3A^KD cells. h Increment of erlotinib sensitivity was also noted in ATAD3A^KD cells