Role Of Kinase NLK In Colon Cancer

The incidence of colorectal cancer ranks third in the world,and it has caused tremendous harm to human health.It is extremely urgent to explore the molecular mechanism of its occurrence and development.In this article,we have selected colorectal cancer tissues and cells to study.NLK is a serine/threonine protein kinase with high homology to both MAPK and CDK.Similar to MAPK and CDK,NLK is involved in the regulation of multiple signaling pathways.From invertebrate worms to humans,NLK is highly evolutionarily conservative.Additionaly,from invertebrates to mice and humans,NLK is associated with many phenotypes and diseases that are not yet fully understood.Therefore,exploring new NLK-regulated signaling pathways and functions not only help us to understand phenotypes associated with NLK,but also provide a solid theoretical basis for future prevention and treatment of NLK-related diseases.This study found the role and mechanism of NLK in the malignant development of colorectal cancer.And our results suggested that NLK is most likely to be involved in TGF-β signaling pathway.Transforming growth factor beta(TGF-β)is a multifunctional cytokine in the transforming growth factor superfamily.And,TGF-(3 is secreted by various cell types,including macrophages.Furthermore,the TGF-β superfamily includes endogenous growth-inhibitory proteins,and increased TGF-β expression is often associated with malignancy in many cancers and defects in the cytostatic response to TGF-p.Firstly,we examined the expression levels of NLK in cancer tissues and adjacent tissues and found that NLK was lowly expressed in cancer tissues.Further,by plotting the growth curves of NLK-overexpressed SW48 and wild-type SW48,it was found that NLK has an effect of promoting cell proliferation.Cell migration experiments demonstrated that NLK inhibited cell migration.Using CRISPR/Cas9 knockout NLK gene,Smad2 expression was significantly reduced.In addition,the amount of NEDD9 increased in NLK knockout cells.When the gradient of NEDD9 expression increased,the expression of Smad2 decreased in a gradient.Thus,NEDD9 is antagonistic to Smad2.Moreover,the overexpression of NEDD9 and the low expression of Smad2 are related to cell migration.Therefore,NLK may inhibit phenotype of migration by changing the expression levels of Smad2 and NEDD9.