Conclusions
PRRX1A, but not PRRX1B, was demonstrated to have important roles in the regulation of the stemness and metastatic potential of lung cancer, which suggests the potential application of PRRX1A in cancer treatment.
Methods
In vitro and in vivo experiments were employed to investigate the molecular mechanism. Using CSCs, mouse models, and clinical tissues, we obtained a general picture of the relatively higher level of PRRX1A compared to PRRX1B, and PRRX1A thus promoting EMT and maintaining stemness of CSCs.
Results
PRRX1A but not PRRX1B was upregulated in lung cancer tissues and was positively correlated with TGF-β expression. In CSCs, overexpressed PRRX1A promoted malignant behaviors via transcriptional activation of TGF-β depending on TGF-β/TGF-βR signaling pathway. PRRX1A knockdown decreased self-renewal capacity accompanied by a decrease in stemness factor expression independent of the TGF-β/TGF-βR signaling pathway. Furthermore, PRRX1A was found to tightly bind to and stabilize SOX2. PRRX1A promoted sphere formation not only by enhancing stemness via stabilizing SOX2 but also by promoting cell proliferation. Conclusions: PRRX1A, but not PRRX1B, was demonstrated to have important roles in the regulation of the stemness and metastatic potential of lung cancer, which suggests the potential application of PRRX1A in cancer treatment.