SPP1 and non-small cell lung carcinoma: Based on these results, we suggest that TM4SF4 up-regulates OPN expression by triggering the GSK3β/β-catenin signaling pathway and that secreted OPN persistently activates the JAK2/STAT3 pathway or via SRC/FAK/STAT3 pathway autocrine signaling for EMT-associated CSC-like properties in NSCLC cells (Figure 6).