New target for cancer potential - RUNX2.

Cancer cells develop with many genes that become overactive, while others are reduced in expression.
these genetic changes help the tumor grow out of control, make it more invasive, and adapt to changing circumstances, eventually causing the tumor metastasis to spread to other parts of the body.
study, published July 23 in the journal Cancer Cell, researchers from the Massachusetts Institute of Technology and Harvard University described structural changes in a series of chromatin that control the evolution of cancer cells.
study of lung tumors in mice, the researchers identified 11 chromatin states (also known as osteogenome states) when cancer cells became more aggressive.
researchers believe that the key molecule RUNX2 found in the chromatin state of more aggressive tumor cells is associated with advanced lung cancer in humans and could be used as a biomarker to predict a patient's prognostics.
: "This work is an example of the first time that single-celled esoteric genomic data have been used to fully map tumor evolution regulatory genes in cancer," said lead author Dr Lindsay LaFave of Cancer Cell.
" controlling role Of the cell's genome, which contains all the genetic material of the cell, plays a key role in determining which genes are expressed.
each cell's genome has an ontogenous genetic modification, such as proteins and compounds attached to DNA, and these substances do not alter the DNA sequence.
modification varies by cell type, affecting the expression characteristics of genes and the differentiation of different types of cells, such as lung cells and neurons.
have also been suggested that preso-genetic changes can affect cancer progression.
study, the team analyzed changes in the metastases that occur with the development of lung tumors in mice.
study was a mouse model of lung adenocarcinoma, which is caused by two specific genetic mutations that can better summarize the development of lung tumors in humans. Using a new technique previously developed by Dr. Jason Buenrostro, one of the paper's co-authors, for single-celled oscic genomic analysis, the
team analyzed the oscic genetic changes that occur in tumor cells from the early stages to the more invasive stages, and examined tumor cells transferred outside the lungs.
Based on the location of the oscic genetic changes and the density of chromatin, this analysis revealed 11 different chromatin states in cancer cells (below), and that cells in these 11 states may exist in a single tumor, suggesting that cancer cells can follow different evolutionary pathways.
photo source: Cancer Cell researchers also determined the corresponding changes in the location of transcription factors binding to chromosomes in each chromatin state.
when transcription factors bind to the initiator region of a gene, the transcription of the mRNA of the gene is initiated, essentially controlling the activity of the binding gene.
chromosome modification to a certain extent so that the gene's initiators can be combined with transcription factors.
with changes in the chromosome structure of tumor cells, transcription factors tend to target genes that help cancer cells get rid of lung cell "identity" and reduce differentiation.
most tumor cells eventually gain the ability to leave their original position and produce new tumors.
of this process is controlled by the transcription factor RUNX2.
in more aggressive cancer cells, RUNX2 promotes gene transcription of proteins secreted by cells.
these proteins help reshape the environment around the tumor, making it easier for cancer cells to escape (below).
: Cancer Cell researchers also found that these invasive pre-metastasis tumor cells are very similar to those that have metastasised tumor cells.
" suggests that when pre-metastasis tumor cells are located in primary tumors, they actually change their chromatin state to look like metastasis cells and then migrate to the environment.
We believe that these tumor cells can metasn by metastasis and spread to distant locations such as the lymph nodes or liver, thanks to the metastatic genetic changes that occur in these cells in primary tumors.
," Dr. LaFave said.
a new biomarker researchers also compared chromatin states in mouse tumor cells with human lung tumors.
found that the expression of RUNX2 also increased in more invasive human tumors, suggesting that RUNX2 could be used as a biomarker to predict a patient's prognosticity (see figure below).
image Source: Cancer Cell RUNX-positive highly predicts poor survival in lung cancer patients.
, when a patient has early RUNX-positive characteristics, it can also be used to better predict a patient's prognostics.
runX may also be a potential drug target, although drugs that target transcription factors are difficult to design (transcription factors often lack a clear structure that acts as a drug binding site).
researchers are also looking for other potential targets in the metastogenesic genetic changes identified in more aggressive tumor cells.
these targets may include chromosomal regulators, a protein responsible for controlling chromosomal chemical modification.
" chromatin regulatory factors are usually enzymes and therefore more likely to be targeted.
we are also exploring what are the key targets driving these chromatin state transitions and which of them are therapeutically targeted.
," Dr. LaFave said.
reference: 1 s Lindsay M. LaFave et al. Epigenomic State Transitions Projecte Tumor Progression in Mouse Lung Adenocarcinoma. Cancer Cell (2020). 2 s gene-controlling mechanisms play key role in cancer progression (Source: MIT website)