Nuclear expression of phosphorylated TRAF2- and NCK-interacting kinase in hepatocellular carcinoma is associated with poor prognosis

Jin, Jing; Jung, Hae Yoen; Wang, Yuli; Xie, Julie; Yeom, Yong Il; Jang, Ja‐June; Lee, Kyuho

doi:10.1016/j.prp.2013.10.007

Cited by 17 publications

(15 citation statements)

References 21 publications

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“…Numerous studies have reported that β-catenin overexpression in the cytoplasm and/or nucleus is correlated with cancer metastasis and poor prognosis (43)(44)(45)(46)(47)(48)(49)(50)(51). In the present study, higher Edmondson grade, poor TNM stage and positive portal vein invasion cases were identified to have increased cytoplasmic expression of β-catenin.…”

Section: Fak β-Catenin C-met Clinicopathological --------------------supporting

confidence: 55%

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Gong

et al. 2018

Oncol Lett

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Abstract. The present study aimed to investigate the prognostic value of specific molecular markers in patients with hepatocellular carcinoma (HCC) who had received surgery. Immunohistochemical analysis was used to measure the expression of hepatocyte growth factor receptor (c-Met), β-catenin and focal adhesion kinase (FAK) in patients with HCC. c-Met expression was identified to be high in patients with larger tumors, higher α-fetoprotein (AFP) levels, higher Edmondson grades, portal vein invasion and higher tumor-node-metastasis (TNM) stages. FAK expression was high in patients with portal vein invasion, higher Edmondson grades and higher TNM stages. β-catenin expression was high in patients with larger tumors, hepatitis B virus (HBV) infection, portal vein invasion, higher Edmondson grades and higher TNM stages. Following multivariate analysis, FAK (P= 0.002) and β-catenin (P= 0.006) expression levels were demonstrated to be significantly associated with Edmondson grade. Additionally, the tumor size (P= 0.009) and HBV infection status (P= 0.002) were revealed to be associated with β-catenin expression. Kaplan-Meier survival curve analysis demonstrated that patients with HCC with higher FAK expression, higher β-catenin expression, portal vein invasion, higher Edmondson grades, higher TNM stages, younger ages and higher AFP levels had significantly poorer prognoses. Cox's regression analysis revealed that the survival period was correlated with the Edmondson grade, age, AFP level, and FAK and β-catenin expression. Univariate analysis of c-Met, β-catenin and FAK identified a significant correlation between FAK and β-catenin (P= 0.015). Correlation analysis revealed no significant correlation between the three molecular markers, but β-catenin and c-Met were markedly correlated (P=0.052). No significant correlation between FAK, c-Met or β-catenin expression was identified. FAK and β-catenin expression demonstrated a correlation with a range of clinicopathological factors, and high FAK and β-catenin expression levels were identified to be correlated with a poor survival rate of patients with HCC. Thus, patients with higher FAK and β-catenin expression may require more aggressive therapy. The results of the present study suggest that FAK and β-catenin expression possess more prognostic value than c-Met expression in patients with HCC.

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Section: Fak β-Catenin C-met Clinicopathological --------------------supporting

confidence: 55%

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Gong

et al. 2018

Oncol Lett

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“…4E; Supplementary Table S13) included seven enhancers located in introns 1, 3, 7, and 8 of the SLC2A2 gene and four enhancers in introns 9, 10/11, and 25 of the TNIK gene encoding a kinase involved in the Wnt signaling pathway. Nuclear expression of TNIK has been associated with poor HCC prognosis ( Jin et al, 2014). HiCap data also revealed two intergenic enhancers and three enhancers located in introns of genes.…”

Section: Novel Insights On the Pharmacogenetics Of Fluoropyrimidine Tmentioning

confidence: 96%

A Multi-Omics Approach to Liver Diseases: Integration of Single Nuclei Transcriptomics with Proteomics and HiCap Bulk Data in Human Liver

Cavalli

Diamanti

Pan

et al. 2020

OMICS: A Journal of Integrative Biology

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The liver is the largest solid organ and a primary metabolic hub. In recent years, intact cell nuclei were used to perform single-nuclei RNA-seq (snRNA-seq) for tissues difficult to dissociate and for flash-frozen archived tissue samples to discover unknown and rare cell subpopulations. In this study, we performed snRNA-seq of a liver sample to identify subpopulations of cells based on nuclear transcriptomics. In 4282 single nuclei, we detected, on average, 1377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p < 0.05) for 7682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry proteomics for the same liver sample. We observed a reasonable correlation between proteomics and in silico bulk snRNA-seq (r = 0.47) using tissue-independent gene-specific protein abundancy estimation factors. We specifically looked at genes of medical importance. The DPYD gene is involved in the pharmacogenetics of fluoropyrimidine toxicity and some of its variants are analyzed for clinical purposes. We identified a new putative polymorphic regulatory element, which may contribute to variation in toxicity. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and we investigated all known risk genes. We identified a complex regulatory landscape for the SLC2A2 gene with 16 candidate enhancers. Three of them harbor somatic motif breaking and other mutations in HCC in the Pan Cancer Analysis of Whole Genomes dataset and are candidates to contribute to malignancy. Our results highlight the potential of a multi-omics approach in the study of human diseases.

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“…The previous study was reported TNIK were frequently upregulated in high-grade tumors ovarian cancer and serous hepatocellular carcinoma [14]. Moreover, TNIK hyperactivity contributes to Human Lung Adenocarcinoma cell metastasis [13].…”

Section: Discussionmentioning

confidence: 93%

“…and gastric cancer [8][9][10][11][12][13][14][15]. As a kinase, TNIK phosphorylated TCF4 and mediated the activation of Wnt target genes in colorectal cancer growth [8].…”

mentioning

confidence: 99%

TNIK swaths AR to WNT pathway and drives Castration-Resistant Prostate Cancer

Jiang¹,

Guo²,

Wang³

et al. 2020

Preprint

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Background: The development of CRPCa was driven by complex genetic and epigenetic mechanisms that remained poorly understood. TNIK (Traf2 and Nck-interacting kinase) has been reported to be a serine/threonine kinase and associated with tumor cell proliferation or unfavorable cancer behavior. The present study was conducted to investigate the TNIK gene expressions in CRPCa. Methods: Using a microarray approach, we identified higher expression of TNIK in CRPCa. The interaction between AR and H3K27me3 upon TNIK depression was determined through molecular and cell biological methods. Co-immunoprecipitations assays were Performed to confirm that TNIK interacted and phosphorylated with β-catenin in CRPCa cell. Results: Specifically we found AR repressed TNIK gene transcription via forming complex with H3K27me3. TNIK was recruited to promote transcription of Wnt target genes in a β-catenin-dependent manner in C4-2 cells. In vitro binding showed that TNIK directly band and phosphorylated β-catenin. Depletion or mutant of TNIK kinase abrogated β-catenin transcription, highlighting the essential function of TNIK kinase activity in Wnt target gene activation. Conclusions: Our findings revealed a regulatory role of AR in TNIK repressor, TNIK interacted with β-catenin and phosphorylated activaing Wnt pathway to promote CRPCa progression. TNIK may present an attractive candidate for drug targeting in CRPCa.

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Nuclear expression of phosphorylated TRAF2- and NCK-interacting kinase in hepatocellular carcinoma is associated with poor prognosis

Cited by 17 publications

References 21 publications

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

A Multi-Omics Approach to Liver Diseases: Integration of Single Nuclei Transcriptomics with Proteomics and HiCap Bulk Data in Human Liver

TNIK swaths AR to WNT pathway and drives Castration-Resistant Prostate Cancer

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