Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caveolin-1 (Cav-1) is an important structural protein of caveolae and plays an oncogene-like role by influencing protein glycosylation in hepatocellular carcinoma (HCC) cells. However, the mechanism by which Cav-1 promotes invasion and metastasis capacity has not been completely clarified. In this study, we demonstrate that Pofut1 is a fucosyltransferase induced by Cav-1. Mouse Hepa1-6 HCC cells lacking Cav-1 expression exhibited low transcription levels of Pofut1, whereas strong Pofut1 expression was found in high-metastasis-potential Hca-F cells with high levels of Cav-1. Cav-1 activated MAPK signaling and promoted phosphorylation of the transcription factors CREB, Sp1, HNF4A and c-Myc, which bound to the Pofut1 promoter region to induce its transcription. As Notch signaling receptors can be modified with O-fucose by Pofut1, we further showed that Cav-1-induced upregulation of Pofut1 expression activated the Notch pathway and thus enhanced invasion and metastasis by mouse HCC cells in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which Cav-1 promotes tumor metastasis by upregulating expression of Pofut1, suggesting that Cav-1 may function as a new biomarker for HCC.
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PMID:Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma. 3135 29

Hepatitis B virus infection is a major cause of liver diseases including hepatocellular carcinoma (HCC). The viral regulatory protein HBx is essential for viral replication and has been involved in the development of HCC. Recently, we characterized a subset of HCCs that replicate HBV. Our aim was to characterize HBx encoded by the full-length HBV DNA (cccDNA) in HCC and non-HCC liver. HBx genes were amplified and sequenced from eight paired HCC and non-HCC tissues in which HBV cccDNA and pgRNA were both present. Sequence analyses identified twelve amino acid positions mutated between HCC and non-HCC liver, and detected in at least three cases. We next assessed the impact of these mutations on HBx function by testing their transcriptional activity. We examined their ability to rescue the transcription of HBV virus deficient for HBx in differentiated HepaRG cells and to induce Smc5/6 degradation, which is mandatory for viral replication. We assessed their capacity to activate a CREB-dependent reporter. Finally we analyzed their growth suppressive activity using colony formation assays. Our results showed that most HBx variants isolated from HCC retain their ability to support HBV cccDNA transcription and to degrade Smc5/6. Strikingly, HCC specific HBx variants are impaired in their antiproliferative activity, which may be detrimental for tumor growth. In conclusion, in contrast to previous observations that tumor HBx variants lack transcriptional activity, we showed here that HBx variants have retained their ability to counteract Smc5/6 and thus to activate cccDNA transcription although they tend to lose antiproliferative activity.
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PMID:Hepatitis B virus replicating in hepatocellular carcinoma encodes HBx variants with preserved ability to antagonize restriction by Smc5/6. 3160 May 32

Several studies have indicated the biological role of mitochondrial Ca2+ uptake in cancer pathophysiology; however, its implications in predicting the prognosis of hepatocellular carcinoma (HCC) are not yet fully understood. Here, we collected tumor specimens and adjacent normal liver tissues from 354 confirmed HCC patients and analyzed the levels of cyclic adenosine monophosphate (cAMP) responsive element binding protein 1 (CREB), mitochondrial calcium uniporter (MCU), mitochondrial calcium uptake 1 and 2 (MICU1, MICU2) using bioinformatics, qRT-PCR, and immunohistochemistry (IHC), and their relationship with clinicopathological characteristics and prognosis. HCC patients with low CREB/MICU1 and high MCU/MICU2 expression exhibited poor survival rate and prognosis in overall survival (OS) and disease-free survival (DFS) analyses. Low CREB/MICU1 and low MICU1 alone indicated poor prognosis in stage I/II and III/IV patients, respectively. In the poor differentiation/undifferentiation group, low expression of MICU1 indicated poor clinical outcomes. Low CREB/MICU1 expression suggested poor outcomes in patients with or without hepatitis B virus (HBV) infection and poor prognosis in the HCV infection group. In the non- hepatitis C virus (HCV) infection group, low MCU1 indicated a poor prognosis. Multivariate analysis demonstrated that CREB and MICU1 expression showed prognostic significance. This study demonstrates the prognostic significance of CREB, MCU, MICU1, and MICU2, in predicting HCC outcomes. Low CREB/MICU1 and high MCU/MICU2 in HCC tissues are associated with poor prognosis, thus offering a novel perspective in the clinical management for HCC patients.
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PMID:A Novel Biomarker Driving Poor-Prognosis Liver Cancer: Overexpression of the Mitochondrial Calcium Gatekeepers. 3311 28


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