<p>Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3β/N-Cadherin Pathway In Non-Small Cell Lung Cancer</p>

Abstract

High metastasis is a leading risk factor for the survival of non-small cell lung cancer (NSCLC) and epithelial-mesenchymal transition (EMT) is a vital step of metastasis. The expression of novel oncogene with kinase domain (NOK) has been observed in some human malignancies, including non-small cell lung cancer (NSCLC); however, the biological function of NOK in NSCLC remains unclear. In the study, we explored the function of NOK in NSCLC, with an aim to elucidate the relevant underlying mechanisms. Patients and methods: We investigate the expression of NOK, p-Akt, p-GSK-3β, E-cadherin and N-cadherin expression by immunohistochemical analysis using tissue microarrays of 72 paired NSCLC samples of cancerous and adjacent normal tissues. The associations between NOK expression and clinicopathological factors, overall survival, other proteins were assessed. Immunofluorescence analysis of NSCLC tissues was performed to study the location of NOK, Akt and GSK-3β. Up or down-regulated of NOK were conducted in two NSCLC cell lines to analyze its impact on AKT/GSK3β pathway. Results: Statistical analysis revealed NOK expression increased in NSCLC tissues compared with normal tissues (P<0.05). It also showed that low NOK expression were associated with a higher possibility of non-lymphatic metastasis, an early pN stage and clinical stage (P<0.05). Moreover, NOK expression was positively correlated with the expression of oncogene p-Akt (Thr308), p-GSK-3β (Ser9) and N-cadherin (P<0.05). Immunofluorescence analysis of NSCLC tissues revealed that NOK is co-located with Akt and GSK-3β. Further study in NSCLC cell lines revealed that NOK overexpression can activate the AKT/GSK3β pathway. Conversely, knockdown of NOK can suppress the AKT/GSK3β pathway. Conclusion: Our results suggest that NOK overexpression correlated significantly with lymphatic metastasis, advanced pN and clinical stage in NSCLC. And NOK may promote EMT by activating the AKT/GSK3β/N-cadherin pathway in NSCLC.

EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion

“…CTNNB1 is generally considered as an intermediate regulator molecule of the FGF19-FGFR4 signaling pathway [ 28 , 36 , 37 , 38 ]. In addition, a lot of studies have shown that the downregulation of CTNNB1 was associated with the downregulations of CDH2, ALCAM and ICAM1, which is consistent with our results [ 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. The extracellular FGF19-FGFR4 signaling pathway mediates the expression of cell adhesion molecules and regulates specific tumorigenic events, including cancer cell proliferation and metastasis, by activating the expression of downstream intracellular genes [ 35 , 49 , 50 ].…”

“…Studies have shown that the FGF19-FGFR4 signaling pathway was an effective antitumor target via mediating a lot of intracellular molecules [ 52 , 53 ]. CTNNB1 as an intermediate molecule between the FGF19-FGF4 signaling pathway and adhesion molecules such as ICAM1, CDH2 and ALCAM [ 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 58 ] was downregulated after EPS364 treatment. Hence, we speculated that EPS364 might target the FGF19-FGF4 signaling pathway to regulate the expression of adhesion molecules.…”

Downregulation of GLUT3 impairs STYK1/NOK‑mediated metabolic reprogramming and proliferation in NIH‑3T3 cells

“…The present study demonstrated that knockdown of GLUT3 diminished cell proliferation and migration driven by STYK1/NOK, demonstrating that GLUT3 may be crucial to STYK1/NOK-mediated malignant transformation and tumorigenesis. Notably, a considerable number of studies have suggested that STYK1/NOK can activate various proliferation-related signaling pathways or molecules (31)(32)(33). A number of the signaling pathways have been reported to strictly regulate the expression and subcellular distribution of GLUTs, for instance, PI3K/Akt/mTOR, hypoxia-inducible factor-1, c-myc and tumor suppressor protein p53 (19,(34)(35)(36), which provides clues for the further exploration of the upstream molecular mechanism of GLUT3 in STYK1/NOK-overexpressing cells.…”

LncRNA RNCR3 Promotes the Progression of HCC by Activating the Akt/GSK3β Signaling Pathway

“…GSK-3 has been shown to regulate cyclin D1 proteolysis and subcellular localization, thereby affecting cell cycle and cell proliferation [ 19 ]. Moreover, GSK-3 can also affect the expression of EMT-related genes, thereby regulating cell migration and invasion [ 20 ]. Therefore, we believe that RNCR3 can promote the proliferation, migration, invasion, growth, and metastasis of HCC cells by activating the Akt/GSK3 β signaling pathway.…”