High Novel Oncogene with Kinase-Domain (NOK) Gene Expression is Associated with the Progression of Renal Cell Carcinoma

Cao, Qingfei; Chen, Meixue; Li, Zizhi; Huang, Weichao; Jin, Yanyang; Ye, Xiongjun; Tong, Ming

doi:10.7754/clin.lab.2015.150626

Cited by 5 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Xu et al suggested that the anti-tumor activities of acyldepsipeptides are dependent on the down-regulated expressions of cyclin D1, CDK4, and PCNA, along with the decreased expression of phosphorylated ERK1/2 in renal 786-O and 769-P cells [125]. Restraining the activation of ERK1/2 suppressed cellular proliferation and migration in an RCC cell line (786-0), this suggested that ERK1/2 may play important roles as a positive regulator to RCC [126].…”

Section: Erk1/2mentioning

confidence: 99%

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Luo

Shi

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs) are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2), the c-Jun N-terminal kinases (JNK), p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1). Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

show abstract

Section: Erk1/2mentioning

confidence: 99%

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Luo

Shi

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Expression of STYK1 (serine/threonine/tyrosine kinase 1, also known as NOK, a novel oncogene with kinase-domain) is aberrant in many malignancies ( Moriai et al, 2006 ; Jackson et al, 2009 ; Kondoh et al, 2009 ; Orang et al, 2014 ; Chen et al, 2016 , 2017 ; Hu et al, 2018 ). Moreover, overexpressed STYK1 likely stimulates cancer development by sustaining proliferative signaling, leading to abnormal proliferation of cancer cells ( Chung et al, 2009 ; Cao et al, 2016 ; Chen et al, 2016 ), enhancing the resistance of tumor cells to programmed cell death ( Lai et al, 2019 ; Shi et al, 2019 ), promoting the Warburg effect, remodeling cellular energetics in malignant cells ( Shi et al, 2017 ; Zhao et al, 2017 ), and stimulating angiogenesis and lymphangiogenesis during tumor progression ( Liu et al, 2016 ). In addition, a high level of STYK1 downregulates the expression of E-cadherin ( Chen et al, 2005 , 2017 ) and induces EMT via MAPK/ERK and PI3K/AKT signaling ( Chen et al, 2016 , 2017 ; Wang et al, 2016 ), indicating that STYK1 expression correlates with EMT and metastasis, although the precise mechanisms underpinning this relationship need to be further studied.…”

Section: Introductionmentioning

confidence: 99%

STYK1/NOK Promotes Metastasis and Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer by Suppressing FoxO1 Signaling

Lai

Lin

Wang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

AimsSerine/threonine/tyrosine kinase 1 (STYK1) has been previously shown to have oncogenic properties, and emerging evidence suggests that STYK1 expression correlates with epithelial-mesenchymal transition (EMT). However, the mechanism of STYK1 involvement in oncogenesis remains unknown. The present study aimed to elucidate how STYK1 expression level relates to the metastasis, migration, invasion, and EMT in non-small cell lung cancer (NSCLC) and to determine the molecular mechanism of STYK1 effects.MethodsSerine/threonine/tyrosine kinase 1 (STYK1) expression level and its relationship with the prognosis of NSCLC were determined using the ONCOMINE database and clinical cases. Non-small cell lung cancer cell lines with the overexpression or knockdown of STYK1 were established to determine whether STYK1 promotes cell migration, invasion, and EMT in vitro and in vivo. In addition, a constitutively active FoxO1 mutant (FoxO1AAA) was used to examine the role of FoxO1 in the STYK1-mediated upregulation of metastasis and EMT in NSCLC.ResultsSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC tissues and cell lines, and its overexpression correlated with poor prognosis in patients with NSCLC after surgery. Enhanced expression of STYK1 potentiated the migration, invasion, and EMT in SW900 cells, thereby promoting metastasis, whereas knockdown of STYK1 inhibited these cellular phenomena in Calu-1 cells. Furthermore, STYK1 expression was positively related to the level of phosphorylated-FoxO1, whereas the constitutively active FoxO1 mutant protected against the positive effect of STYK1 overexpression on cell migration, invasion, and EMT.ConclusionSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC and correlated with poor clinical outcomes. In addition, STYK1 suppressed FoxO1 functions, thereby promoting metastasis and EMT in NSCLC.

show abstract

“…Aberrant expression of NOK has been found in a wide range of cancers, including lung, ovarian, breast, colorectal, prostate, and renal cell cancers. [11][12][13][14][15][16] Recently, NOK was found to be capable of promoting the malignant transformation of tumors in some cancers by activating the PI3K/AKT pathway. 17,18 All these studies indicate that NOK overexpression is associated with cancer progression, and NOK can induce EMT by activating the Akt pathway.…”

Section: Introductionmentioning

confidence: 99%

<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>

Huang

Xiong

et al. 2019

OTT

View full text Add to dashboard Cite

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.

show abstract

High Novel Oncogene with Kinase-Domain (NOK) Gene Expression is Associated with the Progression of Renal Cell Carcinoma

Cited by 5 publications

References 0 publications

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

STYK1/NOK Promotes Metastasis and Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer by Suppressing FoxO1 Signaling

<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>

Contact Info

Product

Resources

About