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
Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital
Highly precise wiring in the Cerebral Cortex
21.09.2017 | Max-Planck-Institut für Hirnforschung
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
21.09.2017 | Physics and Astronomy
21.09.2017 | Life Sciences
21.09.2017 | Health and Medicine