How can cancer cells use hydrogen peroxide to strive?
Hydrogen peroxide (H2O2) is a well-known antiseptic used in our homes since the 1920s. But did you know that our cells produce this molecule and that at low concentrations H2O2instructs our cells to do different things, acting as a signaling molecule? In fact, H2O2may oxidize several cellular components including proteins, altering their function. Healthy cells use H2O2to regulate several of their behaviors, including proliferation, migration, or even cell-to-cell communication. It is, therefore, not surprising that cancer cells produce higher amounts of this reactive oxygen species and take advantage of this signaling feature of H2O2to increase their proliferation and migration,.
Although the knowledge around this subject has been increasing in the past few years, it is still largely unknown which molecules are oxidized by H2O2and how this oxidation affects their function. In our recent work, we have found that a protein called Ribosomal Protein SA (RPSA) is oxidized by H2O2and that this oxidation enhances cancer properties. In fact, RPSA oxidation improves cell adhesion efficiency to the extracellular matrix and promotes cell extravasation (the passing of cells from the blood stream to surrounding tissues, a critical step in the metastatic process). The effect on cell adhesion is most likely mediated by RPSA clusters that accumulate at the cell membrane level and contain specific adhesion molecules called integrins. Interestingly, it appears that different adhesion molecules are present on those clusters depending on the RPSA redox state, suggesting that RPSA oxidation may influence the type of extracellular matrix to which cells adhere.
Our results unravel a new mechanism by which H2O2modulates the cell adhesion properties and identify RPSA as the H2O2sensor in this process. Elevated levels of H2O2produced both in primary tumors and secondary metastatic sites, together with RPSA up-regulation, might confer a selective advantage to tumor cells in the metastatic process by contributing to alterations in cell adhesion properties such as binding specificity. The identification of redox-regulated proteins, such as RPSA and the determination of their relevance in tumor development will be essential to design more specific and efficient redox-based therapies for cancer.
Filipe Vilas-BoasandCarla Real
Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa
Lisboa, Portugal
Publication
Hydrogen peroxide regulates cell adhesion through the redox sensor RPSA.
Vilas-Boas F, Bagulho A, Tenente R, Teixeira VH, Martins G, da Costa G, Jerónimo A, Cordeiro C, Machuqueiro M, Real C.
Free Radical Biology & Medicine. 2015 Nov 18
Related Articles:
Short hydrogen bonds in proteins and their quantum…The assembly of linear polypeptide chains into functional three-dimensional protein architectures involves a unique force called hydrogen bonding. A typical hydrogen bond forms when the donor and acceptor groups approach… | |
Why photobiomodulation therapy is helpful for diabetic wound…It is an obvious well-known issue that diabetic wounds are poorly healing, but the molecular and cellular alterations leading to this impairment is not clear. Many studies concluded the dysfunction… | |
Murburn concept explains why oxygen is acutely needed to…Murburn concept (from “mured burning”, signifying a restricted uncontrolled oxidative process) provides a tangible rationale why oxygen is so quintessential for immediate maintenance of life-order. It postulates that oxygen-centered diffusible… | |
The roles of mesenchymal stem cells secretome in diabetic…There has been a fourfold rise in the number of diabetics from 108 million in 1980 to 422 million in 2014 and by 2040 the number will reach to 642… | |
BioID screen for bacterial virulence proteins: new tools for…The discovery of penicillin in the 1920s revolutionized our ability to treat bacterial infection. However despite the introduction of antibiotics, infectious bacterial pathogens remain an immense challenge for the healthcare… | |
Insight into the needs of thyroid cancer patients before…The thyroid is a butterfly-shaped gland in the neck below the Adam’s apple. It produces hormones that help influence our metabolism and normal development. Over the last 30 years, the… |
Leave a Reply
You must belogged into post a comment.