BGU researchers find promising target for cancer treatment
The researchers have only studied the mechanism in breast cancer models so far, but are currently expanding it to other cancer types as well
The secret to healing what ails you lies within your own DNA (photo credit: DREAMSTIME)
Researchers from the Ben-Gurion University of the Negev have
discovered a novel mechanism which is a promising target for cancer
therapeutics to optimize cancer treatment, according to a new study published in the peer-reviewed journal Science Advances on Wednesday.
The researchers focused on studying processes in the cell which
regulate cancer initiation and progression, specifically gene
expression, a multistep process in which genes are transcripted,
spliced, translated and eventually lead to a phenotype, an observable
trait.
The study found that BRD4, which has a fundamental role in
regulation gene expression, inhibits the expression of genes which are
involved in translation, in which messenger RNA (MRNA) is translated to a
protein, and can abolish protein synthesis, the process through which
cells make proteins.
BRD4 methylation, a process that can affect the activity of a DNA
segment without changing the sequence, determines the recruitment of the
transcription factor E2F1, which regulates DNA transcription on
selected target genes which are involved in protein generation, a
molecular mechanism which facilitates the balanced expression of these
genes. Un-balanced gene expression could lead to increased proliferation
and transformation which can then lead to the initiation and
progression of cancer.
"Our understanding of human cancer progression and treatment
largely depends on our ability to scientifically explore and deeply
decipher the different cellular events which control these processes,"
said Prof. Dan Levy, a scientist at BGU and the National Institute for Biotechnology in the Negev.
"A central process which regulates cancer pathology is gene expression,
or in other words, what are the mechanisms which turns a gene on or off?
Can we control a selective gene expression to obtain a delicate balance
in cancer-related cellular processes? Can we direct specific cellular
factors to regulate this process? Obtaining such a balance will enable
the cell to decide which genes to activate in a given time and tissue
which will subsequently determine if a cell will become malignant or
not," added Levy.
The researchers have only studied the mechanism in breast cancer models
so far, but are currently expanding it to other cancer types as well,
such as melanoma and glioblastoma, according to Levy. The lab headed by
Levy is studying additional protein methylation pathways, such as cell
cycles and programmed cell death.
“These pathways and others have a direct effect on the development
of diseases such as different types of cancer and metabolic diseases
like diabetes, fatty liver, obesity etc.," said Levy.
"Our
research has great potential for the identification of new therapeutic
targets. Indeed, our research group deals with the development of
specific molecules to modulate the enzymatic and cellular activity of
SETD6 and other methyltransferases. Such agents might be used in the
future for the generation of therapy strategies," added the professor.
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