G9a Promotes Invasion and Metastasis of Non-Small Cell Lung Cancer through Enhancing Focal Adhesion Kinase Activation via NF-κB Signaling Pathway

Potential roles of euchromatic histone methyltransferase 2 (EHMT2 or G9a) in invasion and metastasis aren’t well understood in non-small cell cancer of the lung (NSCLC). Here, we investigated the result and underlying mechanisms of G9a and therapeutic implications of targeting G9a within the invasion and metastasis of NSCLC. Overexpression of G9a considerably enhanced in vitro proliferation and invasion, while knockdown of G9a drastically covered up in vivo growth and metastasis of A549 and H1299 NSCLC cells. Knockdown or inhibition of G9a considerably decreased the expression of focal adhesion kinase (FAK) protein and activation of FAK path. Additionally, defactinib, a powerful FAK inhibitor, partly abolished the G9a-enhanced invasion during these NSCLC cells.

In addition, targeting G9a was discovered to suppress NF-?B transcriptional activity in NSCLC cells through stabilizing NF-?B inhibitor alpha (I?Ba), while an NF-?B inhibitor Parthenilide partly abolished the G9a-enhanced FAK activation, which implies that G9a-enhanced invasion and activation of FAK is mediated by elevated NF-?B activity. Particularly, a powerful positive correlation between your IHC staining of G9a and phosphorylated FAK proteins was identified in H1299 xenografts and 159 installments of NSCLC tissues (R = .408). IMPLICATIONS: The findings of the study strongly show G9a may promote invasion and metastasis of NSCLC cells by enhancing FAK signaling path via elevating NF-?B transcriptional activity, indicating potential Defactinib significance and therapeutic implications of those pathways within the invasion and metastasis of NSCLCs that overexpress G9a protein.