Tumor cells can exploit a cellular program that promotes cell migration and reduces adhesion between cells to spread to distant sites in the body. This cellular program, known as the epithelial-mesenchymal transition, requires large-scale cell movement during embryonic development, tissue remodeling and wound healing. Tumor cells take over this developmental program for their cell movement during invasion and metastasis.
In this EMT process, expression of a cell-to-cell adhesion molecule called E-cadherin, which functions as a “molecular glue” that binds cells to one another, needs to be downregulated in order for cells to disassociate from each other and spread throughout the body. A protein called Snail acts as a master switch in the cell's nucleus to suppress E-cadherin expression and induce EMT in the cell. However, how Snail achieves this task remains unclear. Understanding this molecular mechanism will help to develop novel agents to disrupt this EMT event for treating metastatic breast cancer.
The study, recently published online in the Journal of Clinical Investigation, identified that Snail interacted with a chromatin modifying enzyme G9a and recruited G9a to the E-cadherin promoter. This action closes the gene structure of E-cadherin and thus results in the suppression of “molecular glue” E-cadherin expression. The findings establish that the interaction of Snail with G9a is an important determinant of metastasis in triple-negative breast cancer.
"This finding has significant clinical ramification, because chemical compounds or agents that can disrupt the interaction of Snail with G9a will have a great therapeutic potential of treating triple-negative breast cancer," said UK's Peter Zhou, principal investigator for the study. "Investigators at the Markey Cancer Center are currently exploring this idea and are keen to develop drugs that can treat triple-negative breast cancer."
Triple-negative breast cancer is the worst subtype of breast cancer. This subtype of breast cancer has poor clinical outcome due to the early metastasis of tumor cells and the lack of specific drugs that target it.
"An understanding of the mechanism underlying the biology of metastasis in triple-negative breast cancer will provide novel therapeutic approaches to combat this life-threatening disease," Zhou said.
MEDIA CONTACT: Allison Perry, (859) 323-2399 or firstname.lastname@example.org
Allison Perry | EurekAlert!
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy