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H1.0 loss is a feature of cancer stem cells

H1.0 histone cancer stem cell protein antibody

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#1 whcaroline



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Posted 23 November 2016 - 12:13 AM

Cancer stem cells make it hard to treat cancer because they can lead to cancer treatment resistance, recurrence and development of metastasis. To develop therapy targeted to cancer stem cells, first you should understand the features of these cells. Now, in the latest issue of Science, a team of researchers report a way to attack cancer stem cells. The multinational research, led by Dr Paola Scaffidi from The Francis Crick Institute, London, reveals a mechanism about how cancer cells survive treatment.
Cancer arises from clonal expansion of a single cell. But cells in a tumor are not exactly the same. They may possess different features. Cancer stem cells (CSCs) are rare immortal cells within a tumor that can both self-renew by dividing and give rise to all cell types found in a tumor. Only CSCs have the potential to form new tumors.
Some CSCs can stay alive during and after treatment, and they are responsible for cancer recurrence and metastasis. So it is important to identify the features that distinguish CSCs from other cell types in tumors.
Scaffidi's team and collaborators searched for epigenetic mechanisms that determine which cancer cells can have unlimited proliferative potential. The results showed that CSCs lose the major chromatin protein linker histone H1.0. The protein H1.0 facilitates DNA packaging, and it can silence the genes it binds to.
In further research, the team explored the interaction between H1.0 and DNA, and discovered that H1.0 attaches to the regulatory regions of genes. H1.0 loss results in the activation of the genes that support cancer cell self-renewal. In summary, the study showed that low levels of H1.0 promotes cell division while high levels of H1.0 inhibits cell division. H1.0 protein may determine which cells within a tumor can sustain the long-term cancer growth.
Eran Meshorer, co-author of the study, noted that the absence of H1.0 is a feature of CSCs. The researchers also noticed that cancer patients who expressed reduced overall H1.0 levels showed worse outcome compared with those expressing higher H1.0 levels.
Furthermore, reexpression of H1.0 in tumor cells establishes transcriptional programs that restrict cancer cells' long-term proliferative potential and drive their differentiation. These results indicated that restoration of high H1.0 levels in cancer cells may help block long-term survival ability of cancer cells and thus prevent cancer metastasis and reccurence.
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