Glycosylation-related Diagnostic and Therapeutic Drug Target Markers in Hepatocellular Carcinoma

Watson, Michel E; Diepeveen, Luke A.; Stubbs, Keith A.; Yeoh, George

doi:10.15403/jgld.2014.1121.243.mew

Cited by 17 publications

(23 citation statements)

References 91 publications

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“…As is known, migration is crucial for HCC progression [ 32 ]. In this study, we further analyzed the effect of IRAK1 activity on HCC migration.…”

Section: Resultsmentioning

confidence: 99%

Targeting interleukin-1 receptor-associated kinase 1 for human hepatocellular carcinoma

Jiang

et al. 2016

J Exp Clin Cancer Res

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BackgroundInterleukin-1 receptor associated kinase 1 (IRAK1), as a down-stream of toll-like receptor (TLR) signaling, plays important roles in series of malignancies. However, the role of IRAK1 in hepatocellular carcinoma (HCC) remains little known.MethodsIn our study, reverse transcription-PCR (RT-PCR), Western Blot, and immunohistochemical staining were used to assess the mRNA and protein levels of IRAK1 in clinical samples and cell lines. Cell counting assay and flow cytometry were employed to analyze the effect of IRAK1 on cell cycle and apoptosis. Transwell assay was used to study the role of IRAK1 in cell migration. Moreover, subcutaneous xenograft tumor models predict the efficacy of targeting IRAK1 against HCC in vivo.ResultsIRAK1 was over-expressed in HCC tissues and cell lines. Suppression of IRAK1 by small interference RNA (siRNA) or a pharmaceutical IRAK1/4 inhibitor impeded cell growth, induced apoptosis and lessened HCC xenograft tumor growth. Particularly, IRAK1/4 inhibitor treatment caused G1/S cell cycle arrest and apoptosis, confirming IRAK1 as a new therapeutic target for HCC.ConclusionIRAK1 promotes cell proliferation and protects against apoptosis in HCC, and can be a novel target for HCC treatment.

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“…As is known, migration is crucial for HCC progression [ 32 ]. In this study, we further analyzed the effect of IRAK1 activity on HCC migration.…”

Section: Resultsmentioning

confidence: 99%

Targeting interleukin-1 receptor-associated kinase 1 for human hepatocellular carcinoma

Jiang

et al. 2016

J Exp Clin Cancer Res

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“…Although advances have been made in HCC diagnosis and treatment, patient prognosis is poor [15–18]. Sorafenib, the first and only approved targeted therapy for HCC was developed to disrupt the Ras-Raf-MEK1/2-ERK1/2 signaling pathway by specifically targeting Raf-1 kinase and its chemotherapeutic efficacy was correlated with inhibition of MEK and ERK phosphorylation, and other receptor tyrosine kinases, such as VEGFR-2 and 3 [19–21].…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of eukaryotic translation initiation factor 3H is associated with proliferation, invasion and tumorigenicity in human hepatocellular carcinoma

Zhu

Zeng

et al. 2016

Oncotarget

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AimWe studied the role of eukaryotic translation initiation factor 3 subunit H (EIF3H) in hepatocellular carcinoma (HCC) progression.ResultsHigh EIF3H expression was observed in 50.23% patients. Upregulation of EIF3H is an independent predictor for greater rates of cancer recurrence and shorter overall survival in HCC patients. Knockdown of EIF3H expression in HCC cells promoted apoptosis, and inhibited cell growth, colony formation, migration, as well as xenograft growth. TGF-βand MAPK pathways are potentially targeted by EIF3H.MethodsEIF3H mRNA expression was measured in HCC tissue samples and paired non-tumor samples (N=60) and results were validated in another dataset of 215 HCC patients. Then EIF3H expression and clinical outcomes were correlated. Malignant phenotypes were studied after EIF3H expression was knocked down with siRNA in HCC cell lines. EIF3H targeted pathways were identified by microarray analysis.ConclusionEIF3H is frequently upregulated and is an independent prognostic marker for HCC patients and EIF3H inhibition mitigates the malignant phenotype. Our data provide novel insight into the function of EIF3H in HCC progression, and suggest that EIF3H may be a potentially valuable biomarker for HCC.

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“…An emerging theory in recent years is that the existence of cancer stem cells is the basic cause of the post-operative recurrence of liver tumors (8). The main obstacle is that these cancer stem cells are often in a state of dormancy which impairs the treatment effects of chemotherapeutic drugs (9). Some recent studies have shown that the herpes simplex virus thymidine kinase (HSVtk) gene and the complementary treatment with ganciclovir (GCV) exert marked antitumor effects against HCC by promoting apoptosis and inhibiting angiogenesis (10,11).…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 SUMOylation improves gap junction functions between liver cancer stem cells and enhances their sensitivity to HSVtk/GCV

Shen

et al. 2018

Int J Oncol

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Connexin 43 (Cx43) can be modified and regulated by small ubiquitin-like modifier (SUMO)1; however, its role in liver cancer stem cells is poorly understood. In this study, we found a significant difference in the expression of Cx43 and SUMO1 between cancer stem cells and non-cancer stem cells in liver cancer. In liver cancer stem cells, Cx43 was almost absent, although the level of SUMO1 was significantly higher than that in non-cancer stem cells. Further experiments confirmed that the conjugated site of Cx43 by SUMO1 was located in Lys-144 and Lys-237, both of which are highly conserved among species. By the co-expression of Cx43 and SUMO1 in cancer stem cells, the gap junction intercellular communication (GJIC) of liver cancer stem cells was obviously improved. Using this feature, we verified whether it could effectively increase the sensitivity of cancer stem cells to the herpes simplex virus 1 thymidine kinase (HSVtk) gene in combination with ganciclovir (GCV), a conventional chemotherapeutic drug, in vitro and in vivo. As expected, increasing the expression of Cx43 SUMOylation in liver cancer stem cells effectively enhanced their sensitivity to HSVtk/GCV. On the whole, this study revealed a novel method which may be used to effectively restore GJIC in cancer stem cells in liver cancer, which enhances their sensitivity to conventional chemotherapeutic drugs.

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Glycosylation-related Diagnostic and Therapeutic Drug Target Markers in Hepatocellular Carcinoma

Cited by 17 publications

References 91 publications

Targeting interleukin-1 receptor-associated kinase 1 for human hepatocellular carcinoma

Targeting interleukin-1 receptor-associated kinase 1 for human hepatocellular carcinoma

Elevated expression of eukaryotic translation initiation factor 3H is associated with proliferation, invasion and tumorigenicity in human hepatocellular carcinoma

Connexin 43 SUMOylation improves gap junction functions between liver cancer stem cells and enhances their sensitivity to HSVtk/GCV

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