Liver Kinase B1 Suppresses The Metastasis And Angiogenesis Of Lung Cancer:Involvement Of The Shh Signaling Pathway

Objective:Lung cancer is one of the most common malignant tumors in the world and is generally classified into small cell lung cancer or non-small cell Lung cancer(NSCLC).NSCLC includes large cell carcinoma,adenocarcinoma,squamous cell carcinoma,etc.,clinically accounting for 80%-85% of lung cancer metastasis is an important feature of cancer deterioration,which is the cause of death in nearly 90% of lung cancer patients.Liver kinase B1(LKB1),also known as serine/threonine kinase 11,is a serine/threonine kinase with a nuclear localization signal and a kinase domain.LKB1 is a multifunctional protein involved in cell proliferation,metastasis,cell polarity and energy metabolism.AMP-activated protein kinase is the main downstream target of LKB1,through which LKB1 activates various functions and functions.Hepatic kinase B1(LKB1)has been shown to be closely related to cancer.Although the mechanism behind it is still unknown.In this experiment,we explored the biological behavior of LKB1 in non-small cell lung cancer,further revealing the possible mechanism of action of LKB1.Our study provides a potential theoretical and practical basis for the diagnosis and treatment of LKB1 in non-small cell lung cancer.Method:In this study,LKB1 shRNA and overexpression plasmids were used to transfect and screen stable cells to study the role of LKB1 in lung cancer cells.The involvement of the Shh pathway was detected by western blot.The effects of LKB1 on non-small cell lung cancer and its mechanism were studied by MTT assay,scratch test,ELISA assay,angiogenesis assay,and Matrigel invasion assay.Result:LKB1 silencing promotes migration,invasion and angiogenesis of non-small cell lung cancer cells,and overexpression of LKB1 inhibits migration,invasion and angiogenesis of non-small cell lung cancer cells.Further studies indicate that LKB1 can inhibit the Shh signaling pathway.The Shh signaling pathway inhibitor cyclopamine reduced the effect of LKB1 silencing,suggesting that LKB1 inhibits NSCLC migration,invasion and angiogenesis by inhibiting the Shh signaling pathway.LKB1 silencing reduced E-cadherin levels,elevated levels of N-cadherin,Vimentin,MMP-2,and MMP-9,inhibiting the EMT process of non-small cell lung cancer.And the above experimental phenomenon can be regulated by a specific Shh pathway inhibitor cyclopamine.Conclusion:LKB1 can inhibit metastasis and angiogenesis in non-small cell lung cancer.LKB1 can inhibit the expression of E-cadherin protein and reduce the expression of N-cadherin,Vimentin,MMP-2 and MMP-9 by inhibiting the Shh pathway,thereby inhibiting the EMT process of non-small cell lung cancer.