The expression and prognostic value of protein tyrosine kinase 6 in early-stage cervical squamous cell cancer

Wang, Xiao Jing; Xiong, Ying; Ma, Ze Biao; Xia, Jian Chuan; Li, Yan Fang

doi:10.1186/s40880-016-0114-2

Cited by 11 publications

(15 citation statements)

References 24 publications

(34 reference statements)

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“…Patient tissue analysis of bladder 62 , cervical 4 , prostate 63 , and non-small cell lung cancer 64 showed that higher expression of BRK is associated with poorer overall survival. Particularly, in cervical 4 , thyroid 65 , and bladder cancer 62 , BRK expression levels are also associated with tumor grade and severity. Interestingly in breast cancer, Aubele et al highlighted in year 2007 and 2008 that BRK appears to be a positive indicator of disease-free survival 66 , 67 .…”

Section: Therapeutic Significancementioning

confidence: 99%

Putting the BRK on breast cancer: From molecular target to therapeutics

et al. 2021

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BR east tumor K inase (BRK, also known as PTK6) is a non-receptor tyrosine kinase that is highly expressed in breast carcinomas while having low expression in the normal mammary gland, which hints at the oncogenic nature of this kinase in breast cancer. In the past twenty-six years since the discovery of BRK, an increasing number of studies have strived to understand the cellular roles of BRK in breast cancer. Since then, BRK has been found both in vitro and in vivo to activate a multitude of oncoproteins to promote cell proliferation, metastasis, and cancer development. The compelling evidence concerning the oncogenic roles of BRK has also led, since then, to the rapid and exponential development of inhibitors against BRK. This review highlights recent advances in BRK biology in contributing to the “hallmarks of cancer”, as well as BRK's therapeutic significance. Importantly, this review consolidates all known inhibitors of BRK activity and highlights the connection between drug action and BRK-mediated effects. Despite the volume of inhibitors designed against BRK, none have progressed into clinical phase. Understanding the successes and challenges of these inhibitor developments are crucial for the future improvements of new inhibitors that can be clinically relevant.

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Section: Therapeutic Significancementioning

confidence: 99%

Putting the BRK on breast cancer: From molecular target to therapeutics

et al. 2021

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“…The PCR primers sequences of ASF1B are as follows: forward 5′-TGGACAGGAGTTCATCCGAGTG-3′ and reverse 5′-GTCCCAGTTGATATGGAAGCGG-3′. The 2−ÄÄCt (cycle threshold) method were used, where the expression of GADPH was regarded as an endogenous standard to normalize the relative changes in ASF1B expression [5]. Primers for GADPH are as follows: forward 5'-AGAAGGCTGGGGCTCATTTGC-3' and reverse 5'-ACAGTCTTCTGGGTGGCAGTG-3'.…”

Section: Real-time Pcr Analysismentioning

confidence: 99%

“…Moreover, a variety of novel oncogenes have been identi ed as signi cant biomarkers that are associated with unsatisfactory clinical outcome of cervical neoplasm [5][6][7]. However, they are not su ciently powerful to predict clinical outcome, and their clinical applications are limited because of poor sensitivity and speci city.…”

Section: Introductionmentioning

confidence: 99%

Anti-Silencing Function 1B Overexpression Affects Prognosis and Promotes Invasion in Cervical Carcinoma via Activation of Wnt/β-Catenin Signaling Pathway

Zhang

Han

Sun

et al. 2021

Preprint

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Background: Anti-silencing function 1B histone chaperone (ASF1B) has been identified to compensate for growth defects and sensitivity to replication stress. Recent studies demonstrated that ASF1B plays an important role in the tumorigenesis of human cancer. However, its relationship with clinical outcome of cervical carcinoma is unknown. Therefore, we aimed to investigate the expression pattern and clinical significance of ASF1B in cervical cancer and its role in regulating invasion and metastasis of cervical cancer cell lines.Methods: Expression of ASF1B was analyzed in eight cervical cancer cell lines, and eight pairs of cervical cancer samples and the adjacent normal specimens, using real-time PCR and western blotting. Immunohistochemistry was used to analyze ASF1B expression in paraffin-embedded tissues from 147 cervical cancer patients. The association between ASF1B expression levels, clinicopathological parameters, and prognosis was analyzed statistically. Moreover, the biological function and potential mechanism of ASF1B in migration and invasion of cervical cancer cells were investigated by in vitro experiments and Western blotting.Results: ASF1B mRNA and protein levels were overexpressed in cervical cancer cell lines and tissues compared with normal cells and adjacent normal cervical specimens. In paraffin-embedded cervical carcinoma tissues, upregulation of ASF1B protein was identified in 86 (58.5%) of 147 cases, and was remarkably associated with pelvic lymph node metastasis, lymphovascular space involvement, property of surgical margin, FIGO stage, sqaumous cell carcinoma antigen and poor survival. Cox analysis demonstrated that ASF1B expression was an independent risk predictor for survival in patients with cervical carcinoma. Additionally, down-regulation of ASF1B significantly inhibited invasion and migration of cervical cancer cells. Moreover, it was demonstrated that ASF1B regulated the Wnt/β-catenin pathway in cervical carcinoma.Conclusions: This study suggested that ASF1B might serve as a important prognostic biomarker and therapeutic target for patients with cervical carcinoma.

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“…PTK6 expression was first identified in metastatic breast cancer [6][7][8][9] and subsequently detected in several other cancers of the ovary [10], head and neck [11,12], lung [13,14], esophagus [15], cervix [16], bladder [17], pancreas [18] and stomach [19].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of protein tyrosine kinase 6 overexpression in cancers: a meta-analysis

Jeong¹,

Kim²,

Lee³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Protein tyrosine kinase 6 (PTK6) plays an important role in cell proliferation and differentiation. However, the functions of PTK6 appear highly context-dependent and differ depending on the cell type, as well as its intracellular localization. High PTK6 expression in tumor has been associated with poor pathological features and prognosis in some studies, but other studies have reported opposite results. Therefore, we performed this meta-analysis to derive more precise estimations of the association of PTK6 expression with prognosis and clinicopathological features in cancer patients. Methods: We conducted a literature search in PubMed, Ovid MED-LINE, and MEDLINE databases to cover all articles published until June 2021. All 1475 patients from the eight studies were included in the meta-analysis. Because of heterogeneity in PTK6 expression in non-tumor tissues, the included studies were divided into two subgroups according to PTK expression in non-tumor tissues: the low expression subgroup (LESG) or high expression subgroup (HESG). Results: Patients with high PTK expression showed significantly worse overall survival (OS) in LESG (Hazard Ratio (HR) = 2.53 [95% Confidence Interval (CI), 1.68-3.83], p < 0.0001), but significantly better OS in HESG (HR = 0.56 [95% CI, 0.40-0.78], p = 0.0006). PTK6 expression also showed different associations with clinicopathological features, such as advanced T classification, stage, and differentiation according to PTK6 expression in non-tumor tissues. Conclusions: PTK6 expression in tumor was a prognostic factor in patients with various cancers, but the direction of prognosis differs, depending on the degree of PTK6 expression in non-tumor tissues.

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The expression and prognostic value of protein tyrosine kinase 6 in early-stage cervical squamous cell cancer

Cited by 11 publications

References 24 publications

Putting the BRK on breast cancer: From molecular target to therapeutics

Putting the BRK on breast cancer: From molecular target to therapeutics

Anti-Silencing Function 1B Overexpression Affects Prognosis and Promotes Invasion in Cervical Carcinoma via Activation of Wnt/β-Catenin Signaling Pathway

Prognostic value of protein tyrosine kinase 6 overexpression in cancers: a meta-analysis

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