Although inactivation of the APC gene remains the genetic precondition for the development of this type of cancer, mechanical pressure on the colon speeds up carcinogenesis in animal models. And what if the increase if tumor mass were itself the cause of this pressure? This discovery reported in Human Science Frontier Journal opens up new horizons in research into the mechanical sensitivity of tumors.
Cancer stems from alteration in a cell’s genetic material. Yet a single event is not enough to transform a health cell into a cancer cell. Rather, cancer results from a succession of accidents. The APC (adenomatous polyposis coli) gene is mutated in 80% cases of colon cancer. This alteration is often described as the initiator of carcinogenesis. Although the loss of APC is necessary for development of a colon tumor, it is not sufficient. Other perturbations are needed.
At the Institut Curie, the Mechanics and Genetics of Embryo and Tumor Development team headed by Emmanuel Farge(2) is studying the effect of mechanical stress on gene expression during tumor and embryo development. Farge and colleagues recently demonstrated that morphogenetic movements, which occur in early development of Drosophila embryo, trigger expression of the Twist gene, which controls the differentiation of gastric tissues.(3) They have studied the changes induced by mechanical pressure on the expression of the protein ß-catenin and of two oncogenes controlled by it: Myc, which is involved in tumor growth, and Twist, which contributes to the invasiveness of tumors. The deregulation of ß-catenin is often described as being correlated with loss of the APC gene, in development of colon cancer.
What happens when pressure is applied to the colon of a mouse that has already “lost” a copy of the APC gene? Farge and colleagues observed a relocalization of ß-catenin from the cytoplasm towards the nucleus of the cells, followed by activation of the expression of the oncogenes Myc and Twist, which can then play their full part in carcinogenesis. In the absence of one copy of the APC gene, mechanical pressure of the order of magnitude equivalent to that exerted by intestinal transit would therefore stimulate tumor development.
Mechanical stress is therefore likely to affect the gene expression profile in colon cells already carrying an APC mutation. The events leading to formation of a cancer are not only, therefore, the prerogative of genetics: perturbations in the tumor environment can also participate. Mechanical sensitivity thus becomes a player in carcinogenesis.
So, while the mutation of the APC gene initiates tumor development, growth in tumor mass could accelerate development by compressing neighboring tissues.
Not all then is purely “genetic” or “cellular” in the development of the colon cancer and certain stages could result from mechanical effects. This discovery should prompt reassessment of preventive and therapeutic approaches, at least in colon cancer, and even in oncology in general.(1) Genes associated with cancers
(3) Tissue deformation modulates Twist expression to determine anterior midgut differentiation in Drosophila embryos, N. Desprat, W. Supatto, PA. Pouille, E. Beaurepaire, E Farge, Developmental Cell, September 2008
How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy