Fig. 4.

The silencing of TM4SF1 induces cell cycle G2/M arrest, apoptosis and affects DDR1 signaling and apoptotic markers in NSCLC cell lines. a Representative distribution of A549 and H1299 cell lines both in NC and TM4SF1 silencing cells (left); The distribution and percentage of cells in the G1, S and G2/M phases of the cell cycle are indicated (right).b Knocking down of TM4SF1 sensitized NSCLC cells to cisplatin and paclitaxel, The cell viability was detected by MTS assay after cells were treated with chemotherapy drugs paclitaxel for 24 h or cisplatin for 12 h. All experiments were performed in triplicate, respectively. *p < 0.05, **p < 0.01, ***p < 0.001. c Induction of apoptosis detected by flow cytometric analysis with Annexin V-FITC and PI-staining (right). Quantitative analysis of apoptosis (**p < 0.01, ***p < 0.001). d Expression levels of Casp7, 9, 3, cleaved-PARP were evaluated by western blot in NC and TM4SF1 silencing cells. And the impact of silencing TM4SF1 on the expression of DDR1 and the phosphorylation of its downstream targets AKT, ERK and mTOR. e Inhibitor down-regulated DDR1, mTOR and AKT and Knocking down TM4SF1 can further lower the expression of this pathway after inhibitor treatment