Diagnostic Relevance of Overexpressed Serine Threonine Tyrosine Kinase/Novel Oncogene with Kinase Domain (STYK1/NOK) mRNA in Colorectal Cancer

Orang, Ayla Valinezhad; Safaralizadeh, Reza; Feizi, Mohammad Ali Hosseinpour; Somi, Mohammad Hossein

doi:10.7314/apjcp.2014.15.16.6685

Cited by 15 publications

(16 citation statements)

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“…Due to the potential significance of STYK1 in cancer biology, its clinical relevance in human malignancies has aroused increasing attention. The diagnostic implication of STYK1 mRNA has been demonstrated in cancers of breast, lung and colorectum [ 13 , 14 , 16 ]. In addition, the prognostic value of STYK1 protein expression in non-small cell lung cancer has also been revealed [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…To date, only one study investigated the expression of STYK1 in CRC. Using 36 pairs of CRC tissues, Orang AV et al performed qRT-PCR analysis and found that STYK1 mRNA expression was significantly elevated in cancerous tissues when compared to matched adjacent non-cancerous counterparts [ 16 ]. Nevertheless, the prognostic significance of STYK1 expression has not been assessed in CRC.…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant expression of STYK1 has been previously documented in human malignancies of the breast, lung, ovary, blood, and prostate [ 10 , 11 , 13 - 15 ], and recently, Orang AV et al also reported the significant up-regulation of STYK1 mRNA in CRC tissues [ 16 ]. Thus, as an oncogene, STYK1 could be a candidate biomarker for tumor diagnosis and prognosis prediction.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, as an oncogene, STYK1 could be a candidate biomarker for tumor diagnosis and prognosis prediction. It has been showed that STYK1 mRNA might be a tool to support the diagnosis of breast, lung, and colorectal carcinomas [ 13 , 14 , 16 ]. In addition, the prognostic and therapeutic significance of STYK1 overexpression in human malignant diseases has also been revealed.…”

Section: Introductionmentioning

confidence: 99%

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Serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal cancer

Chen

Cai

et al. 2015

BMC Cancer

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BackgroundAberrant expression of serine threonine tyrosine kinase 1 (STYK1) has been reported in several human malignancies including colorectal cancer (CRC). However, the prognostic significance of STYK1 expression in CRC remains unknown.MethodsSTYK1 protein expression in paraffin-embedded CRC specimens was determined immunohistochemically. The correlation of STYK1 expression with clinicopathologic features was assessed in a cohort containing 353 patients with primary CRC. Kaplan-Meier and Cox proportional regression analyses were used to evaluate the association between STYK1 expression and patients’ survival.ResultsSTYK1 expression was frequently up-regulated in CRC clinical samples at the protein levels and was significantly associated with tumor differentiation grade (p = 0.030), lymph node metastasis (p = 0.004), TNM stage (p = 0.007) and patient death (p < 0.001). Kaplan-Meier analysis indicated that patients with high intratumoral STYK1 expression had a significantly shorter disease-specific survival (DSS) than those with low expression (p < 0.001). Importantly, high levels of STYK1 protein predicted poor DSS for both stage II (p < 0.001) and stage III (p = 0.004) patients. Furthermore, multivariate analyses revealed that STYK1 protein expression was an independent prognostic indicator for both stage II (hazard ratio [HR], 2.472; p = 0.001) and stage III (HR, 2.001; p = 0.004) patients.ConclusionsOur results suggest that increased STYK1 protein expression correlates with disease progression and metastasis and may serve as a predictor of poor survival in CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1285-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal cancer

Chen

Cai

et al. 2015

BMC Cancer

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“…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

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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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SMAD3 inducing the transcription of STYK1 to promote the EMT process and improve the tolerance of ovarian carcinoma cells to paclitaxel

Shi

Zhang

Liu

et al. 2019

J of Cellular Biochemistry

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Objective: To figure out the relationship between SMAD3 and serine-threonine tyrosine kinase (STYK1) in ovarian carcinoma cell's paclitaxel resistance. Methods:The quantitative reverse transcription-polymerase chain reactpostion and Western blot analysis were used to analyze RNA and protein content of SMAD3 and STYK1, respectively. The chromatin immunoprecipitation assay was used to confirm the binding site of SMAD3 to the STYK1 promoter region. Transwell assay was used to detect cell invasion and migration, and WesternBlot was used to detect the marker proteins (vimentin and E-cadherin) of epithelial-mesenchymal transition (EMT) process. MTT and apoptosis assay were used to, respectively, measure cell vitality and apoptosis. In vivo experiments, rats were subcutaneously implanted with A2780 cells to establish an animal model of ovarian cancer and the survival curve was drawn.Results: Upregulating SMAD3 induced the expression of STYK1 in ovarian cancer cell lines. STYK1 is a direct transcriptional target of SMAD3.Upregulating STYK1 improved the paclitaxel resistance of ovarian carcinoma cells. Upregulating STYK1 promoted cell invasion, migration, and the EMT process, and SMAD3 had the same effect with STYK1 on cell invasion, cell migration, and the EMT process. The animal assay showed that downregulating STYK1 inhibited the EMT process and the paclitaxel resistance, further promoting the treatment of cervical cancer. Conclusion: SMAD3 combined with the promoter region of STYK1 to promote the transcription process of STYK1, thereby promoting the EMT process and paclitaxel resistance of ovarian cancer cells. K E Y W O R D SEMT process, ovarian carcinoma, paclitaxel tolerance, SMAD3, Serine threonine tyrosine kinase (STYK1)

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Diagnostic Relevance of Overexpressed Serine Threonine Tyrosine Kinase/Novel Oncogene with Kinase Domain (STYK1/NOK) mRNA in Colorectal Cancer

Cited by 15 publications

References 30 publications

Serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal cancer

Serine threonine tyrosine kinase 1 is a potential prognostic marker in colorectal 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>

SMAD3 inducing the transcription of STYK1 to promote the EMT process and improve the tolerance of ovarian carcinoma cells to paclitaxel

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