According to the researchers, it is becoming increasingly accepted that changes that do not affect the genetic blueprint or DNA sequence, known as the epigenetic landscape, play a major role in defining the properties of normal as well as the cancer cells. While specific epigenetic alterations have been associated with cancer progression, the molecular mediators that ensure transmission of these reversible alterations to successive tumor cells has been elusive.
The BUSM researchers found that the disruption of TGFâ signaling caused a corresponding decrease in the promoter DNA binding activity of DNA methyl transferase 1 leading to passive demethylation of the newly synthesized DNA resulting in expression of genes that are silenced during breast cancer progression.
"The re-expression of genes that promote cell adhesion in cancer cells upon inhibition of the Smad signaling pathway causes reversal of tumorigenic properties and puts the brakes on cancer progression," said principal investigator, Sam Thiagalingam, PhD, an associate professor of medicine and pathology and a member of the Cancer Research Center at BUSM. "This study may pave the way to discovering other pathways and network of events that are responsible for sustaining epigenetic memory in cancer and cancer stem cells and could lead to the unraveling of effective targets for eradication of tumor cells as well as tumor initiating cells," he added.
"While targeting of TGFâ and TGFâ receptors have been actively pursued for cancer therapy, the current finding may introduce a new spin on the wheel and lead to the development of new therapeutic strategies for late stage breast and other cancers by the direct perturbation of the Smad signaling pathway," explained lead author Panos Papageorgis, PhD, a post-doctoral fellow in the genetics program at BUSM.
Funding for this study was provided by the Susan G. Komen for Cure and the National Institutes of Health.
Gina DiGravio | EurekAlert!
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Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
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In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
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