Gene/Protein
Disease
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: UNIPROT:Q86TM3 (
cage
)
29,987
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Global loss of DNA methylation is frequently observed in the genome of human tumors. Although this epigenetic alteration is clearly associated with cancer progression, the way it exerts its pro-tumoral effect remains incompletely understood. A remarkable consequence of DNA hypomethylation in tumors is the aberrant activation of "cancer-germline" genes (also known as "cancer-testis" genes), which comprise a diverse group of germline-specific genes that use DNA methylation as a primary mechanism for repression in normal somatic tissues. Here we review the evidence that such cancer-germline genes contribute to key processes of tumor development. Notably, several cancer-germline genes were found to stimulate oncogenic pathways involved in cell proliferation (SSX, DDX43, MAEL, PIWIL1), angiogenesis (
DDX53
), immortality (BORIS/
CTCFL
), and metastasis (CT-GABRA3). Others appear to inhibit tumor suppressor pathways, including those controlling growth inhibition signals (MAGEA11, MAGEB2), apoptosis (MAGEA2, MAGEC2), and genome integrity (HORMAD1, NXF2). Cancer-germline genes were also implicated in the regulation of tumor metabolism (MAGEA3/MAGEA6). Together, our survey substantiates the concept that DNA hypomethylation promotes tumorigenesis via transcriptional activation of oncogenes. Importantly, considering their highly restricted pattern of expression, cancer-germline genes may represent valuable targets for the development of anti-cancer therapies with limited side effects.
...
PMID:Oncogenic roles of DNA hypomethylation through the activation of cancer-germline genes. 2834 86
High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecologic cancer-related death. We have previously shown that
CTCFL
(also known as
BORIS
,
B
rother
o
f the
R
egulator of
I
mprinted
S
ites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed
BORIS
in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC.
BORIS
-expressing cells exhibited increased motility and invasion, and
BORIS
expression was associated with alterations in several
cancer-associated gene
expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly,
GALNT14
, a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and
GALNT14
knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition,
in silico
analyses provided evidence for
BORIS
and
GALNT14
coexpression in several cancers. Finally, ChIP-seq demonstrated that expression of
BORIS
was associated with
de novo
and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including
GALNT14
. Taken together, our data indicate that
BORIS
may promote cell motility and invasion in HGSC via upregulation of
GALNT14
, and suggests
BORIS
as a potential therapeutic target in this malignancy. IMPLICATIONS: These studies provide evidence that aberrant expression of BORIS may play a role in the progression to HGSC by enhancing the migratory and invasive properties of FTSEC.
...
PMID:
BORIS
Expression in Ovarian Cancer Precursor Cells Alters the CTCF Cistrome and Enhances Invasiveness through
GALNT14
. 3129 1
