Early Detect Many Cancer Types in Blood Test

Scientists from University of Oxford have indicated that a new-found anti-cancer protein named ASPPS could control and reverse epithelial cells' changes of shape and motion state. This finding would be very important in the study of wound healing, embryonic development, and cancer metastasis. This study was published in Nature Cell biology.

Epithelial to mesenchymal transition(EMT) and the reverse, mesenchymal to epithelial transition(MET), provide cellular plasticity during development, wound healing and cancer metastasis. EMT is associated with enhanced cell migration and invasion and requires a disruption of apical-basal polarity and loss of E-cadherin expression. MET is required for nephrogenesis, and defects in MET result in kidney fibrosis. In addition, ASPP2 was first identified as a tumor suppressor and an activator of the p53 family. Its downregulation is associated with metastasis of human breast cancer and head and neck cancer, and poor prognosis in diffuse large B-cell lymphomas.

In this study, researchers have identified ASSP2 as a molecular switch of MET and EMT.ASPP2 contributes to MET in mouse kidney in vivo. Mechnistically, ASPP2 induces MET through its PAR3-binding amino-terminus, independently of p53 binding. ASPP2 prevents?-catenin from transactivating ZEB1, directly by forming an ASPP2-?-catenin-E-cadherin ternary complex and indirectly by inhibiting?-catenin's N-terminal phosphorylation to stabilize the?-catenin-E-cadherin ternary complex. ASSP2 limits the pro-invasive property of oncogenic RAS and inhibits tumour metastasis in vivo. Reduced ASSP2 expression results in EMT, and is associated with poor survival in hepatocellular carcinoma and breast cancer patients.

Therefore, ASPP2 is a key regular of epithelial plasticity that connects cell polarity to the suppression of WNT signaling, and tumor metastasis.

Epithelial to mesenchymal transition(Emt) and the reverse, mesenchymal to epithelial transition(MET), provide cellular plasticity during development, wound healing and cancer metastasis. EMT is associated with enhanced cell migration and invasion and requires a disruption of apical-basal polarity and loss of E-cadherin expression. MET is required for nephrogenesis, and defects in MET result in kidney fibrosis. In addition, ASPP2 was first identified as a tumor suppressor and an activator of the p53 family. Its downregulation is associated with metastasis of human breast cancer and head and neck cancer, and poor prognosis in diffuse large B-cell lymphomas.

Scientists have developed a way to identify important cancer mutations. This approach can mode the effects that cancer mutations have on the intricate patterns of communication between groups of proteins involved in cell signaling. Using this tool, researchers can get a better understanding of how mutations can alter signaling networks.

To find meaning in the rising oceans of genomic data, scientists, from the new Laboratory of Systems Pharmacology, have created multidimensional models and applied them to the genome-wide studies. The models show that specific mutations somehow alter the social networks of proteins in cells. From this they can deduce which mutations among the numerous mutations present in cancer cells might actually play a role in driving disease.

Find driver mutations

Many of the most widely studied cancer genes, such as P53 and Ras, were discovered after decades of work by many groups. But today, in the era of high throughput genomics, there are thousands of times more data than previously existed, showing that the sheer volume of catalogued cancer mutations is vast.

Not all mutations actually influence tumor behavior. In order to distinguish the drivers, researchers use a kind of "polling" strategy in which the most common mutations--deduced as the significant ones--can be identified. Only the most promising candidates are then subjected to the detailed analysis in the fields of cancer biomarker and molecular diagnostics.

For every common mutation, there are approximately four rare ones, so, based on numbers, rare mutations might be much more significant than previously suspected. Some researchers consider a large universe of rare mutations to be dark matter. A study, published in the journal Nature Genetics, shows that all this dark matter actually matters.

The researchers found that mutations are not really the blunt force that they expected. An altered protein cause a subtle, almost surgically precise, altering of the communication pathway, rather than knocking out an entire branch of a network or inserting an entirely new character.

From the perspective of the mutation, it is hard to be so precise, but cancer can't be too disruptive, or else it might die. This subtle altering of networks achieves that objective. Drug companies can exploit this and possibly develop more targeted therapies.