Like people, cells in the human body protect their personal space. They seem to know how much space they need, and if it gets too tight, most cells prefer to break free. The mechanism enabling cells to evade crowded environments appears to involve an unusual player - the cell nucleus. This is what researchers showed in their recent wook in the journal Science.
The human body consists of trillions of cells growing in confined volumes, which often leads to cell crowding. The crowding effect is exacerbated when cell growth and proliferation are out of control during tumor formation. This creates a compressive microenvironment for the constituent cells. How do tumor cells cope with the lack of space and compressive stresses? Answering this question, the investigators found that the cells are able to sense environmental compression.
To do so, they utilize their largest and stiffest internal compartment, the nucleus. Squeezing cells to the degree that physically deforms the nucleus causes the nuclear membranes to unfold and stretch. These changes are detected by specialized proteins, activating cellular contractility. The ability to develop contractile forces helps squeezing the cell out of its compressive microenvironment in an "evasion reflex" mechanism. Therefore, the study proposes that the nucleus operates as a ruler (see the accompanying illustration). It allows living cells to measure their personal space and trigger specific responses once the space becomes violated.
As the scientists describe in the paper, Ca2+-dependent phospholipase cPLA2 is a protein, which senses nuclear membrane stretch upon cell compression. The lead author emphasizes that cPLA2 represents a druggable target. "Pharmaceutical companies are currently testing small molecule inhibitors of cPLA2. Based on our data, downregulating the activity of cPLA2 in tumor cells might interfere with their ability to escape the primary tumor and metastasize to distant locations", explains the author.
cPLA2-inhibitors prevent the production of arachidonic acid (ARA), which subsequently affects cell migration, growth, and survival. However, ARA can also be obtained by cells from their environment. The Western diet, for instance, is a potent source of omega-6 fatty acids, such as ARA. Dietary fat restriction and consumption of omega-3 instead of omega-6 fatty acids could synergize with cPLA2 inhibitors to effectively attenuate tumor cell escape from overcrowded areas. "Testing these hypotheses is an exciting direction for future research", concludes the author.
Identifying the cell nucleus as an active player that rapidly converts mechanical inputs into signaling or metabolic outputs is surprising. Until today, the nucleus was considered as a passive storehouse for genetic material. "We are very excited about what comes next", says the author. According to the author, high degrees of nuclear deformation could be predictive of metastatic potential and resistance to chemotherapy and immunotherapy.
"For many years, pathologists have been evaluating changes in the shape of the nucleus to discriminate between different stages of tumor growth; however, how these structural-mechanical alterations of the nucleus functionally impact cancer cells remained completely unexplored", says the author.
https://science.ccri.at/2020/10/16/how-cancer-cells-escape-crowded-tumor/
https://science.sciencemag.org/content/370/6514/eaba2894
Nuclear machanoconduction in cancer metastasis
- 932 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Harmful protein waste in the muscle from a genetic disorder
Read more
Natural selection opposes sexual selection
Read more
Largescale brain epigenetics study discovers 84 new genes linked to…
Read more
Rescuing the synapse at nerve-muscle junction with antibody therapy
Read more
Controlling neuronal hyperactivity in Bourneville's tuberous sclero…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar