Identification of genes conferring resistance to 5-fluorouracil

Yoo, Byoung Kwon; Gredler, Rachel; Vozhilla, Nicollaq; Su, Zao-zhong; Dong, Chen; Forcier, Talitha; Shah, Khalid; Saxena, Utsav; Hansen, Ulla; Fisher, Paul B.; Sarkar, Devanand

doi:10.1073/pnas.0901451106

Cited by 135 publications

(142 citation statements)

References 50 publications

Supporting

Mentioning

134

Contrasting

Order By: Relevance

“…Genes involved in tumorigenesis have been also found to contribute to chemoresistance of hepatocellular carcinoma (13,15,22,23). Identification of hepatocellular carcinoma-associated targets is thus critical not only for understanding the molecular mechanisms of both intrinsic and acquired chemoresistance but also for developing hepatocellular carcinoma-associated targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Guo

et al. 2014

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Chemoresistance is one of the major obstacles in systemic chemotherapy and targeted therapy for patients with advanced hepatocellular carcinoma. To identify novel chemoresistance-associated targets in hepatocellular carcinoma, chemoresistant hepatocellular carcinoma cell lines were established. By comparing the global gene expression profiles between chemoresistant and chemosensitive cell lines, eight novel chemoresistance-associated genes were identified to be significantly associated with the commonly augmented chemoresistance of hepatocellular carcinoma cells. One upregulated candidate named transmembrane protein 98 (TMEM98) was found to be overexpressed in 80 of 118 (67.80%) of patients with hepatocellular carcinoma. TMEM98 mRNA in tumor tissues was significantly higher than nontumor tissues of patients with hepatocellular carcinoma (P < 0.0001). Upregulation of TMEM98 was significantly correlated with advanced tumor stage (P ¼ 0.048), high incidence of early tumor recurrence (P ¼ 0.005), poor overall survival (P ¼ 0.029), and poor disease-free survival (P ¼ 0.011) of patients with hepatocellular carcinoma after hepatectomy. Importantly, upregulation of TMEM98 mRNA in patients with hepatocellular carcinoma who received transarterial chemoembolization (TACE) treatment was significantly higher than in patients without TACE treatment (P ¼ 0.046). Moreover, patients with poor response to TACE treatment had higher degree of TMEM98 upregulation than the responsive patients. In vitro and in vivo studies showed that suppression of TMEM98 in chemoresistant hepatocellular carcinoma cells restored their chemosensitivity, while forced overexpression of TMEM98 enhanced their chemoresistance. The mechanism of TMEM98 in conferring chemoresistance of hepatocellular carcinoma might be possibly through activation of the AKT pathway and deactivation of p53. In conclusion, we identified a panel of novel common chemoresistance-associated genes and demonstrated that TMEM98 is a chemoresistanceconferring gene in hepatocellular carcinoma. Mol Cancer Ther; 13(5); 1285-97. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Guo

et al. 2014

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…It was demonstrated that MTDH enhances the expression of dihydropyrimidine dehydrogenase (DPYD), which catalyzes the initial and rate-limiting step in the catabolism of 5-FU, which is an adjuvant and palliative chemotherapeutic agent that is frequently used in the treatment of patients with HCC (44). In addition, MTDH augments the expression of the transcription factor LSF, which regulates the expression of thymidylate synthase (TS), a target of 5-FU.…”

Section: Mtdh Expression ----------------------------------------------mentioning

confidence: 99%

Prognostic significance of metadherin overexpression in hepatitis B virus-related hepatocellular carcinoma

et al. 2012

View full text Add to dashboard Cite

Abstract. Metadherin (MTDH), which is an HIV-1 or TNF-α-inducible transcript, has a crucial role in several types of cancer by regulating multiple cellular signaling processes. However, to date, the role of MTDH in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is still unclear. In the present study, we detected MTDH expression in normal liver, chronic hepatitis B and HBV-related HCC tissues. The data showed that MTDH expression levels were elevated in the hepatitis B tissues and especially in the HBV-related HCC tissues compared to normal liver tissues. There was a trend for gradually increased MTDH expression from normal liver tissue to hepatitis B and HBV-related HCC tissues. Furthermore, a statistical analysis revealed that MTDH expression significantly correlated with the American Joint Committee on Cancer (AJCC, 7th edition) stage (P=0.020), T classification (P= 0.007), N classification (P= 0.044), vascular invasion (P=0.006) and histological differentiation (P=0.020) in the HBV-related HCC patients. In addition, patients with high MTDH levels had shorter survival times compared to those with low MTDH expression (P=0.001). Taken together, these results suggest that MTDH could be a potential prognostic marker for overall survival and tumor progression and a chemotherapeutic target in HBV-related HCC patients.

show abstract

“…The plasmid constructs carrying shRNA (pSUPER-EGFP-MTDH) against MTDH were performed as previously described (Kock et al, 2007;Yoo et al, 2009). …”

Section: Plasmid Construction and Transfectionmentioning

confidence: 99%

A polysaccharide from Huaier induced apoptosis in MCF-7 breast cancer cells via down-regulation of MTDH protein

Luo

Xiong

et al. 2016

Carbohydrate Polymers

View full text Add to dashboard Cite

Identification of genes conferring resistance to 5-fluorouracil

Cited by 135 publications

References 50 publications

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Identification of Transmembrane Protein 98 as a Novel Chemoresistance-Conferring Gene in Hepatocellular Carcinoma

Prognostic significance of metadherin overexpression in hepatitis B virus-related hepatocellular carcinoma

A polysaccharide from Huaier induced apoptosis in MCF-7 breast cancer cells via down-regulation of MTDH protein

Contact Info

Product

Resources

About