Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0345904 (
liver cancer
)
15,188
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Liver organogenesis and cancerogenesis share common mechanisms. HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Less is known about the involvement of HOX genes with liver cancerogenesis. The comparison of the HOX gene network expression between nontumorous livers and hepatocellular carcinomas (HCCs) highlights significant differences in the locus A HOX genes, located on chromosome 7, with a consistent overexpression of HOXA13 mRNA thus validating this gene deregulation as a feature of HCC. HOXA13 is a determinant of gut primordia and posterior body structures. Transcriptome analysis of HCC/nontumorous liver mRNAs, selected on the basis of HOXA13 overexpression, recognizes a set of deregulated genes. The matching of these genes with previously reported HCC transcriptome analysis identifies cell-cycle and nuclear pore-related HCC phenotype displaying poor prognosis. HOXA13 and HOXA7 homeoproteins share a consensus sequence that physically links
eIF4E
nuclear bodies acting on the export of specific mRNAs (c-myc, FGF-2, vascular endothelial growth factor (VEGF), ornithine decarboxylase (ODC) and cyclin D1). We report the protein-protein interaction between HOXA13 and
eIF4E
in
liver cancer
cells and the deregulation of
eIF4E
mRNA and protein in cell cycle/nuclear pore HCC group phenotype and in T4 stage HCCs, respectively. Thus, transcriptional and post-transcriptional HOXA13 deregulation is involved in HCC possibly through the mRNA nuclear export of
eIF4E
-dependent transcripts.
...
PMID:The HOX gene network in hepatocellular carcinoma. 2162 5
The proline rich homeodomain protein (PRH), also known as haematopoietically expressed homeobox (HHEX), is an essential transcription factor in embryonic development and in the adult. The PRH protein forms oligomeric complexes that bind to tandemly repeated PRH recognition sequences within or at a distance from PRH-target genes and recruit a variety of PRH-interacting proteins. PRH can also bind to other transcription factors and co-regulate specific target genes either directly through DNA binding, or indirectly through effects on the activity of its partner proteins. In addition, like some other homeodomain proteins, PRH can regulate the translation of specific mRNAs. Altered PRH expression and altered PRH intracellular localisation, are associated with breast cancer,
liver cancer
and thyroid cancer and some subtypes of leukaemia. This is consistent with the involvement of multiple PRH-interacting proteins, including the oncoprotein c-Myc, translation initiation factor 4E (
eIF4E
), and the promyelocytic leukaemia protein (PML), in the control of cell proliferation and cell survival. Similarly, multiple PRH target genes, including the genes encoding vascular endothelial growth factor (VEGF), VEGF receptors, Endoglin, and Goosecoid, are known to be important in the control of cell proliferation and cell survival and/or the regulation of cell migration and invasion. In this review, we summarise the evidence that implicates PRH in tumourigenesis and we review the data that suggests PRH levels could be useful in cancer prognosis and in the choice of treatment options.
...
PMID:Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion. 2687 67
Cancer cells develop mechanisms to escape immunosurveillance, among which modulating the expression of immune suppressive messenger RNAs is most well-documented. However, how this is molecularly achieved remains largely unresolved. Here, we develop an in vivo mouse model of
liver cancer
to study oncogene cooperation in immunosurveillance. We show that MYC overexpression (MYC
Tg
) synergizes with KRAS
G12D
to induce an aggressive liver tumor leading to metastasis formation and reduced mouse survival compared with KRAS
G12D
alone. Genome-wide ribosomal footprinting of MYC
Tg
;KRAS
G12
tumors compared with KRAS
G12D
revealed potential alterations in translation of mRNAs, including programmed-death-ligand 1 (PD-L1). Further analysis revealed that PD-L1 translation is repressed in KRAS
G12D
tumors by functional, non-canonical upstream open reading frames in its 5' untranslated region, which is bypassed in MYC
Tg
;KRAS
G12D
tumors to evade immune attack. We show that this mechanism of PD-L1 translational upregulation was effectively targeted by a potent, clinical compound that inhibits
eIF4E
phosphorylation, eFT508, which reverses the aggressive and metastatic characteristics of MYC
Tg
;KRAS
G12D
tumors. Together, these studies reveal how immune-checkpoint proteins are manipulated by distinct oncogenes at the level of mRNA translation, which can be exploited for new immunotherapies.
...
PMID:Translation control of the immune checkpoint in cancer and its therapeutic targeting. 3064 86
Angiogenesis and the activation of AKT/mTOR pathway are crucial for hepatocarcinoma development and progression, the activation of mTORC1/2 and relevant substrates have been confirmed in clinical hepatocarcinoma samples. Therefore, AKT/mTOR pathway represents the major targets for anti-cancer drugs development. Here, we investigated the anti-proliferative activity and mechanisms of ZJQ-24 in hepatocellular carcinoma, both in vivo and in vitro. A hepatocellular carcinoma xenograft model showed that ZJQ-24 significantly inhibited tumor growth with few side effects. MTT assays, flow cytometric analysis, Western blotting and immunohistochemistry identified that ZJQ-24 effectively suppressed hepatocellular carcinoma cell proliferation via G
2
/M phase arrest and caspase-dependent apoptosis but had no cytotoxic on normal cells. Furthermore, ZJQ-24 significantly blocked AKT/mTOR signaling by down-regulation of mTORC1 molecules, including phospho-p70S6K (Thr
389
) and phospho-4EBP-1 (Ser65, Thr
37/46
, Thr
70
) and phospho-AKT (Ser
473
) in
HCC
cells. It is very important that the ZJQ-24 did not induce the mTORC1-depdent PI3K/Akt feedback activation through JNK excitation. Moreover, ZJQ-24 inhibited the cap-dependent translation initiation by impairing the assembly of the
eIF4E
/eIF4G complex. Immunohistochemistry further confirmed ZJQ-24 inhibited the tumor growth through suppression of VEGF and AKT/mTOR pathways in vivo. Thus, the present study is the first to illustrate that ZJQ-24 triggers antiangiogenic activity and apoptosis via inhibiting the AKT/mTOR pathway in hepatocellular carcinoma cells, providing basic scientific evidence that ZJQ-24 shows great potential function as inhibitor of angiogenesis and tumor growth in hepatocellular carcinoma.
...
PMID:Indole hydrazide compound ZJQ-24 inhibits angiogenesis and induces apoptosis cell death through abrogation of AKT/mTOR pathway in hepatocellular carcinoma. 3311 25
