STYK1 promotes cancer cell proliferation and malignant transformation by activating PI3K-AKT pathway in gallbladder carcinoma

Hu, Yunping; Wu, Zengbin; Jiang, Lin; Jin, Yunpeng; Li, Huaifeng; Zhang, Yi-Jian; Ma, Qiang; Ye, Yuanyuan; Wang, Zheng; Liu, Yongchen; Chen, Hongzhuan; Liu, Yingbin

doi:10.1016/j.biocel.2018.01.016

Cited by 20 publications

(25 citation statements)

References 27 publications

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“…We identified six studies7–10,12,13 from public databases (PubMed, Embase, Cochrane Library, Wiley Online Library, Medline). The meta-analysis results indicated that the pooled HR was 2.21 (95% CI =1.81–2.71) for the high vs low STYK1 expression group ( P <0.00001; Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…Serine threonine tyrosine kinase 1 (STYK1), also known as novel oncogene with kinase domain (NOK), is a member of the receptor protein tyrosine kinase (RPTK) family 6. STYK1 expression is high in a wide range of cancers, including gallbladder carcinoma,7 lung cancer,8 colorectal cancer,9 nasopharyngeal carcinoma,10 ovarian cancer,11 pancreatic cancer,12 and hepatocellular carcinoma 13. These data indicate that increased levels of STYK1 expression are associated with progression in the aforementioned cancers.…”

Section: Introductionmentioning

confidence: 99%

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Low STYK1 expression indicates poor prognosis in gastric cancer

Fang¹,

Wang²,

Xiao³

et al. 2018

CMAR

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BackgroundThe expression of serine threonine tyrosine kinase 1 (STYK1), a member of the receptor protein tyrosine kinase (RPTK) family, is abnormal in several cancers. However, the molecular mechanism of STYK1 regulation of gastric cancer (GC) progression is unknown.Materials and methodsWe evaluated STYK1 expression in GC tissues and the corresponding normal tissues. Specimens from 93 patients with GC were examined with immunohistochemical staining. The relationship between STYK1 protein expression and the patients’ clinicopathological features was assessed. Kaplan–Meier and Cox proportional regression analyses were used to evaluate the association between STYK1 expression and survival.ResultsSTYK1 expression was decreased in GC tissues. Low STYK1 expression was significantly associated with poor tumor differentiation (P=0.023), advanced clinical stage (P=0.021), and poor overall survival (OS; P=0.034). Univariate and multivariate analyses revealed that STYK1expression was an independent prognostic indicator (HR =0.53, 95% CI =0.29–0.95, P=0.039; HR =0.51, 95% CI =0.24–0.91, P=0.030, respectively).ConclusionDownregulated STYK1 expression correlated significantly with poor tumor differentiation, advanced clinical stage, and poor OS in GC. STYK1 might be a diagnostic and prognostic indicator in patients with GC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low STYK1 expression indicates poor prognosis in gastric cancer

Fang¹,

Wang²,

Xiao³

et al. 2018

CMAR

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“…Some experimental efforts have shown that NOK could promote the EMT by activating the PI3K/Akt signaling pathway in gallbladder carcinoma and hepatocellular carcinoma. 17,18 In breast cancer, NOK can form a tripartite complex with Akt and GSK3β, and promote the phosphorylation of GSK3β at Ser9, mediated by the phosphorylation of Akt at Thr308. 31 With the phosphorylation at Ser9, the enzymatic activity of GSK3β is inhibited, which results in the upregulation of snail and downregulation of E-cadherin.…”

Section: Discussionmentioning

confidence: 99%

“…[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. However, the pathological function of NOK in the malignant transformation of NSCLC remains unknown.…”

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

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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.

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“…209 Exploiting the same pathway, Nectin-4 and STYK1 promote GBC cell proliferation, metastasis, and tumor growth. 210,211 In addition, ubiquitin protein ligase E3 component N-recognin 5 decreases the degradation of PTEN/PI3K/AKT signal pathway, facilitating tumor growth. 212 Given the growing evidence that lncRNAs emerge to regulate gene expression, a number of laboratories have paid considerable attention in the identification of novel lncRNAs that prompt GBC progression.…”

Section: Her2mentioning

confidence: 99%

Overview of current targeted therapy in gallbladder cancer

Song

et al. 2020

Sig Transduct Target Ther

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Gallbladder cancer (GBC) is rare, but is the most malignant type of biliary tract tumor. Unfortunately, only a small population of cancer patients is acceptable for the surgical resection, the current effective regimen; thus, the high mortality rate has been static for decades. To substantially circumvent the stagnant scenario, a number of therapeutic approaches owing to the creation of advanced technologic measures (e.g., next-generation sequencing, transcriptomics, proteomics) have been intensively innovated, which include targeted therapy, immunotherapy, and nanoparticle-based delivery systems. In the current review, we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC. Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease, ultimately improving the efficacy of treatment.

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STYK1 promotes cancer cell proliferation and malignant transformation by activating PI3K-AKT pathway in gallbladder carcinoma

Cited by 20 publications

References 27 publications

Low STYK1 expression indicates poor prognosis in gastric cancer

Low STYK1 expression indicates poor prognosis in gastric cancer

<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>

Overview of current targeted therapy in gallbladder cancer

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