Targeting the NF-κB pathway may provide therapeutic benefits to patients with basal-like, triple-negative breast cancer


Previously study has been shown that, α-catenin could complex with the IκBα protein, and stabilize IκBα by inhibiting its and its association with the proteasome.

Usually, Aberrant activation of NF-κB signaling is found in triple-negative basal-like breast cancer cells, while the cause of this activation has remained elusive,The NF-κB pathway can be activated by a variety of factors. Activated NF-κB regulates kinds of target genes. Aberrant activation of NF-κB signaling is associated with various human cancers including breast cancer.

Researchers from Texas MD Anderson Cancer Center discovered that, loss of α-catenin as a mechanism by which the NF-kB pathway is activated in the basal-like subtype of breast cancer. This is highly relevant in human tumors, as alpha-catenin is specifically downregulated in human basal-like breast cancer, correlates with recurrence-free survival and negatively correlates with the activity of NF-κB signalling. Thus, Targeting the NF-κB pathway may provide therapeutic benefits to patients with basal-like, triple-negative breast cancer

 Reference: alpha-catenin acts as a tumour suppressor in E-cadherin-negative basal-like breast cancer by inhibiting NF-κB signalling. Nature cell biology, 2014

Microbes and Colon Cancer

The human large bowel is a common site for adenocarcinomas and also one of the most densely populated microbial ecosystems on our planet. Colorectal cancers affect over a quarter of a million people each year. When the disease is local or confined, cure rates range from 70%–90%; however, advanced colorectal cancers has a high mortality rate, consistently ranking in the top three causes of cancer-related death around the globe. There has been long-standing curiosity about the role of bacteria in colorectal carcinogenesis.


Colorectal cancers is essentially a genetic disease,the following graph is showed genetic alterations and the progression of colorectal cancers.

Some models support the hypothesis that the microbe contributes to colon carcinogenesis. Such as, Streptococcus gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis, Escherichia coli and Fusobacterium spp. Specific microbes, a microbial community, or the two acting sequentially and/or in synergy are three models.

Cancer has been called the ‘‘emperor of all maladies’’, and in unraveling the role of the microbiota in colorectal carcinogenesis, research efforts are giving this emperor new clothes and laying him bare. With sufficient research support, the vast genomic and metabolic potential of the gut microbiota may be realized as the most powerful weapon in the 40-plus year war on cancer. Specific species, microbial consortia, and microbial metabolites generated from ingested foodstuffs are all potential targets for decreasing or increasing cancer risk and perhaps even for diagnosis, treatment stratification, and therapy.

Reference: Cynthia L. Sears and Wendy S. Garrett, Cell Host & Microbe, 2014

Marian R.Glancy

What’s the Fate of Structural Biology?


In 1912, the German physicist Max Von Laue published the first paper demonstrating x-ray diffraction from a crystal.

In 1913, William Lawrence Bragg and William Henry Bragg(father and son) determined crystal structure of diamond.

In 1952, Rosalind Franklin used x-ray diffraction to image DNA and suggested it has a helical structure.

In 1958, John Kendrew and Max Perutz determined first protein structures of myoglobin and hemoglobin.

Thousands of structural biologists have worked for a century to solve molecular structures. To date, the Cambridge Structural Database have collected more than 600,000 structures of organic and organometallic molecules and the Protein Data Bank also contained about 100,000 Biological Macromolecular Structures. Based on the data in Protein Data Bank, ~88.5% of Biological Macromolecular Structures were solved by X-ray Crystallography, ~10.5% were solved by NMR and only ~1% were determined by Electron Microscopy. Obviously, structural biology, especially crystallography has made great achievements. UNESCO has declared 2014 to be the International Year of Crystallography

While recently,  The United States is winding down a $1 billion project to churn out protein structures. You can click on the following links to read details:

Structural Biology Scales Down

Large NIH projects cut

Crystallography at 100

What can structural biology bring us? What’s the fate of structural biology?

As we know, Structure Based Drug Design and High Throughput Screening are the two popular strategies in drug discovery and combining these two strategies should be a better choice. Therefore, excellent 3D structures would well advance drug discovery. What’s more, 3D structures of Biological Macromolecular can help us understand many biological phenomena in the atomic level. While, we have to say, using the same method, like crystallography, to determine plenty of structures rather than developing new or perfecting methodologies to overcome the weakness of current structure models. Try to imagine, what would happen if we could capture or even observe the native conformations and entire motion profile of biological macromoleculars. Will the tumor and other devastating diseases still be so terrible?