PTEN represses colon cancer progression

The tumor suppressor gene phosphatase and tensin homolog (PTEN) is frequently mutated in colon cancer. However, the potential contribution of loss of PTEN to colon cancer progression remains unclear.


In this study the research demonstrated that PTEN overexpression or knockdown in Lovo colon cancer cells decreased or increased paxillin expression, respectively. Moreover, paxillin reversed PTEN mediated inhibition of Lovo cell invasion and migration. Overexpression of PTEN in orthotropic colon cancer nude mice model inhibited tumor formation and progression. In addition, PTEN protein level was negatively correlated with that of paxillin in human colon cancer tissues. Mechanistically, they identified three NF-KappaB binding sites on paxillin promoter and confirmed that paxillin was a direct transcriptional target of NF-kappaB.

These findings reveal a novel mechanism by which PTEN inhibits the progression of colon cancer by inhibiting paxillin expression downstream of PI3K/AKT/NF-κB pathway. Thereby, PTEN/PI3K/AKT/NF-κB/paxillin signaling cascade is an attractive therapeutic target for colon cancer progression.


Ling li Zhang, Gang Gang Mu,et al. PTEN represses colon cancer progression through inhibiting paxillin transcription via PI3K/AKT/NF-kB pathway [J].JBC, 2015, doi: 10.1074.

“Rubbish” Gene may Cause Cancer

In the past few years, scientists have achieved significant progresses in the study on the function of non-coding RNAs(IncRNAs). As the important regulatory factor, IncRNAs has been found to play important role in many disease progress including cancer. Researchers from Harvard Medical School have found that a subtype of IncRNA may promote the expression of BRAF and activation of MAPK to cause cancer. This study was published on Cell.


Over the past few years, remarkable progress has been made in establishing long non-coding RNAs as important regulators of various biological processes. Given their critical roles, it is not surprising that aberrant expression and/or function of IncRNAs are implicated in the development of diseases such as cancer.

Pseudogenes, a sub-class of IncRNA genes that developed from proteins, have long been viewed as non-functional genomic relicts of evolution. However, the vast majority of pseudogenes have protein-coding parental counterparts with which they share high sequence homology, which enables pseudogenes to participate in posttranscriptional regulation of their parental genes.

In this study, scientists report that mice engineered to overexpress either the full-length murine B-Raf pseudogene Braf-rs 1 or its pseudo “CDS” or “3′ UTR” develop an aggressive malignancy resembling human diffuse large B cell lymphoma. They show that Braf-rs 1 and its human ortholog, BRAFP1, elicit their oncogenic activity, at least in part, as competitive endogenous RNAs(ceRNAs) that elevate BRAF expression and MAPK activation in vitro and in vivo.

Their engineered mouse models demonstrate the oncogenic potential of pseudogenes and indicate that ceRNA-dediated microRNA sequestration may contribute to the development of cancer.

Reference:Karreth F A, Reschke M, Ruocco A, et al. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo[J]. Cell, 2015.

Low-temperature Plasma in the Treatment of Prostate Cancer

Researchers from University of York has, for the first time, applied the Low-temperature Plasma(LTPs) in the cells which are from patients’ tissue samples. It is said that LTPs may become a potential treatment for prostate cancer. This study was published in British Journal of Cancer.


Despite continual improvement and refinement, long-term treatment for prostate cancer(PCa) is still recognised as inadequate. However, around a third of patients will experience recurrence of their disease following radiotherapy. This may be due to inherent radio-resistance of a small fraction of the tumour-the cancer stem-like cells.

In recent years, Low-temperature plasma(LTPs ) have shown considerable potential as active agents in biomedicine. They are formed by applying a high electric field across a gas, which accelerates electrons into nearby atoms and molecules, leading to a cascade effect of multiple ionisation, excitation and dissociation processes. This creates a complex and unique reactive environment consisting of positive and negative

In this study, scientists first conducted a proof-of-principle study in order to validate the cytopathic effect of LTP treatment on two commonly used prostate cells lines derived from benign disease (BPH-1) and prostate cancer metastasis. They then analyzed in detail the effect of LTP treatment on a matched pair of primary samples. They cultured prostate epithelial cells from normal prostate and prostate cancer tissue. retrieved from biopsies from a single patient, allowing for direct comparison of the effects of LTP on both normal and cancer cells.

The research group presents the first experimental evidence that LTP may be a suitable candidate for focal therapy treatment of patients with early onset prostate cancer through the induction in colony-forming capacity, and ultimately necrotic cell death, in clinically relevant and close-to-patent samples.

Reference:Hirst A M, Simms M S, Mann V M, et al. Low-temperature plasma treatment induces DNA damage leading to necrotic cell death in primary prostate epithelial cells[J]. British journal of cancer, 2015.

Proving Scientific Dogma Isn’t the Whole Story

“I was so amazed by what I was seeing. We repeated and repeated our work to prove that the standard scientific dogma wasn’t the complete story.”

Recently, the University of Pittsburgh Cancer Institute (UPCI) researchers, technical and scientific discovery by an accidental combination, plus a hunch, reveals a previously unseen biological process, which may be associated with certain types of cancer rapid growth related.

 Dr. Shuda and his colleagues found that when cells divide, a well-known cancer protein (called mTOR) – previously thought to be solely responsible for the control of cancer cells in the production of an important protein, called cap-dependent translation (cap -dependent translation) – You can create a different protein resale CDK1. They observed that the process also detects a key viral oncoproteins, make a common, usually harmless virus can convert healthy cells into cancer cells.

Merkel cell polyomavirus (MCV) was found in 2008 by the co-author of this article, Dr. Yuan Chang and Patrick S. Moore. The virus can cause a rare but deadly form of skin cancer, called Merkel cell carcinoma. And then they found a program called “small tumor protein (sT)” viral protein. It may lead to a series of reactions, tumor growth inhibition mTOR protein can resist anticancer drugs.

Dating back to the 1960s in the study, the scientists believe that during cell division, cap-dependent protein synthesis is turned off. New research shows that is not necessarily in the case, and CDK1 possible alternatives mTOR. mTOR and CDK1 works by inhibiting a gated protein (called 4E-BP1, can close the cap-dependent protein synthesis).

Even in very aggressive tumor, there are less than 1% of the cells in the active division cycle, called mitosis, which makes the study of mitotic cells become very difficult. Furthermore, traditionally drugs which used to arrest cell division, can inhibit protein production by CDK1. That may be why the study did not determine CDK1 seems to play an important role before.

Shuda uses a technique called flow cytometry to detect dividing cells. The use of special fluorescent label, he can see mitotic cells completely inactivated protein 4E-BP1 by CDK1. He also directly measured the mitotic process of manufacturing proteins.

Sure enough, even when mTOR is knockout, CDK1 persists, protein synthesis, cell division and make the necessary to proceed.

In this paper, the senior author, Dr. professor of molecular genetics and biochemistry, University of Pittsburgh Moore said: “Now, we can not say that this process involves CDK1 cause cancer – which is the next study we will deal with the problem, but it points to. Cell biology a basic control mechanisms, and brings an interesting possibility to create or combination of anticancer drugs, so that they inhibit the synthesis of mTOR and CDK1-related proteins, may be a useful therapy. “

Breath test ‘could give clues to stomach cancer risk’

A simple breath test could help predict whether people with gut problems are at high risk of developing stomach cancer, an early study shows. It detects chemical compounds in people’s breath, in an attempt to distinguish unique “breath prints” in those with risky pre-cancerous changes.


Scientists believe earlier detection may help improve the prognosis.

The new “nanoarray” breath test builds on earlier work from researchers in Israel, Latvia and China. It relies on the idea that people with cancer may have unique breath signatures – containing minute chemical compounds that are not found in the breath of people free from the illness.

Researchers studied breath samples from 145 patients. Around 30 of these were already known to have stomach cancer. The rest had been referred for investigations because of concerning symptoms. They did not have full-blown cancer – but some had worrying changes that doctors call “pre-cancerous” that could develop into malignancies. Scientists tried out the test on a number of different scenarios. It was fairly good at distinguishing cancerous samples from non-cancerous ones.

And it showed some promise at identifying worrying pre-cancerous changes that were at high risk of developing into the disease. But it was not accurate in every case – some patients were misdiagnosed as being at high risk. Scientists say more work is needed before it is ready to use in clinics.

Dr Emma Smith of Cancer Research UK, said: “Diagnosing cancer in its early stages offers patients the best chance of successful treatment, so research like this has potential to help save lives. “But we would need to be sure the test is sensitive and accurate enough to be used more widely.” Research involving thousands of European patients is now under way.

Crystal structures of the human adiponectin receptors

Adiponectin is a hormone secreted by fat cells, involved in the regulation of glucose and fatty acid oxidation, and played an important role in obesity and diabetes. The researchers hope to reduce diabetes-related deaths by analyze the structure of receptors AdipoR1 and AdipoR2.


It is known that type 1 diabetes and type 2 diabetes in vivo adiponectin levels is relatively low. Studies also show that this hormone can improve glucose intolerance in mice. In addition, shortly before the development of small molecule called AdipoRon capable of simulating adiponectin, adiponectin activation in genetically obese mice receptors, improve glucose intolerance and extend the life of mice.

Adiponectin receptors in mammals, plants, yeast and many other organisms are evolutionarily conserved and that means they have an important biological role. The researchers believe that understanding the mechanism of binding adiponectin receptors contribute to the design of new drugs target to these receptors.

SPring-8 is the world’s highest-energy third-generation synchrotron radiation source, Shigeyuki Yokoyama, Takashi Kadowaki and Toshimasa Yamauchi led the research team used the device to obtain a high-resolution crystal image of adiponectin receptors.

To their surprise, the adiponectin receptor is a new type of structure, and their transmembrane helix is completely different from G protein-coupled receptor and G protein-coupled receptor is currently the most commonly used drug development target. Further research also showed that adiponectin receptors in the integration of a zinc ion, by three histidine residues fixed. The researchers noted that the presence of the large cavity of unknown function of adiponectin receptors. Yokoyama speculated that they may be the inlet and outlet of the substrate, and receptor activity.

“We get a lot of interesting unexpected discovery by analyzing these two important evolutionarily conserved receptors. We believe that the new information adiponectin receptor structure can help us to further understand the relationship between structure and function. This study helps people develop adiponectin targeted receptor drugs, for type II diabetes and other obesity-related diseases for treatment. presence of zinc ions receptor structure makes us particularly interested in understanding the importance of it need to do more work, “Yokoyama said.

Time to change how we think about cancer

One of the most common misconceptions about cancer is that it is one disease. Most people think of cancer as something that will automatically kill you if left alone, but there are so many variations of the disease that this is actually not a given. Every “cancer” is different.


Some aggressive cancers grow rapidly and can be quite serious, but some grow slowly or not at all and may be completely safe to live with. As physicians, we need to help change the way the medical community and general public think about cancer. And World Cancer Day, being marked Wednesday, is as good a day as any to start.

To begin with, we need to be more precise. Science has taught us quite a bit about the disease in the last few decades, so a one-size-fits-all definition is no longer the right fit because there isn’t just one type of cancer — there are many.

It’s like allergies; we can easily understand that there is more than just one type of allergy. Allergies vary hugely in type and severity, and not everyone will lead to anaphylactic shock or a fatality. Some allergies cause no more than itchy eyes or a runny nose. The same principle is true of cancer. And because the term cancer is surrounded by connotations of panic and death, in the case of extremely low-risk lesions, we should reclassify them accordingly.

Participating in clinical trials or registries that allow clinicians to adopt less aggressive approaches to in situ or specific types of invasive cancers is one of the best ways to accomplish this. Clinical trials or registries allow women to participate today in what the standard of care will be tomorrow; they make it possible for us to test and document what we learn so that knowledge can inform the future — and help us differentiate IDLE threats.

Fighting cancer and Ebola with nanoparticles

In medicine, finding a substance that attacks cancerous tumors without destroying the healthy tissue around it has long been the Holy Grail.From targeted remedies such as monoclonal antibodies to surgery, cancer has still managed to elude a treatment that discretely and separately attacks it alone.


Nanotechnologies, however – the manipulation of matter at a molecular and even atomic scale to penetrate living cells — are holding out the promise of opening a new front against deadly conditions from cancer to Ebola.According to Dr Thomas Webster, the chair of chemical engineering atNortheastern University in Boston, research into medical nanotechnology is gaining pace and the medical establishment is starting to sit up and pay attention.

At the core of the technology is the ability to attach drugs, and in some cases metals and minerals, to nanoparticles that would then bind themselves to life threatening cancer cells or viruses.In one study, Dr Webster’s team is developing methods to attach gold nanoparticles to cancer cells.Infrared light would then heat up the nanoparticles, killing the cancer cells with heat but leaving the healthy cells alive to do their job.

“This technology has been studied for the better part of a decade, but we’re looking at ways of making it better,” Dr Webster told CNN. “One that we’ve created in the lab we’ve called ‘nanostars.’”A star shape has a lot more surface area, so they can kill cancer cells faster than a nanosphere because they heat up faster.”Even if it’s carrying a drug, a star has a lot more surface area on which to attach it — it’s got a different morphology.”

While nanoparticle technology still has many years of research ahead of it, nanostructured surfaces are already becoming part of the medical firmament.”These are being approved by the Food and Drug Administration and we’re seeing better bone growth, better tissue growth and we’re seeing the ability to decrease infection using these materials.”

These developments, he said, were helping patients in the here and now.

“What we’re using with this is the same materials that we are implanting today — so titantium for hip implants, polyvinyl chloride for catheters, silicone for breast implants.”We’re doing a lot of work with putting nanofeatures on materials that could stop cancers from coming back.”One successful area, he said, had been the implanting of nanofeatures on catheters; a common vehicle of infection where catheters are often reused.

“We’re taking what’s currently being used, we take it off the shelf, we then figure out a way to put nanofeatures on there and we see significant improvements.”It’s a wonderful way to give an immediate solution to nanomedicine; so that the public, scientists and clinicians can see how nanomedicine can help patients today, not 10 years down the road.”

Cancer Res reveal tumor stem cells regulation signal

Considerable evidence suggests that pro-inflammatory pathways drive self-renewal of cancer stem-like cells (CSC), but the underlying mechanisms remain mainly undefined. Here the study report that the let7 repressor LIN28B and its regulator IKKβ sustain cancer cell stemness by interacting with the Wnt/TCF7L2 (TCF4) signaling pathway to promote cancer progression.


The study found that LIN28B expression correlated with clinical progression and stemness marker expression in breast cancer patients. Functional studies demonstrated that the stemness properties of LIN28B-expressing human breast and lung cancer cells were enhanced by IKKβ, whereas loss of LIN28B abolished stemness properties in these settings. These phenomena were driven through interactions with TCF7L2, which enhanced LIN28B expression by direct binding to intron 1 of the LIN28B gene, which in turn promoted TCF7L2 mRNA translation through a positive feedback loop. Notably, RNAi-mediated silencing of LIN28B or pharmacological inhibition of IKKβ was sufficient to suppress primary and metastatic tumor growth in vivo. Together, these results establish the LIN28B/TCF7L2 interaction loop as a central mediator of cancer stemness driven by pro-inflammatory processes during progression and metastasis, possibly offering a new therapeutic target for generalized interventions in advanced cancers.


Chong Chen, Fengqi Cao, et al. IKKβ enforces a LIN28B/TCF7L2 positive feedback loop that promotes cancer cell stemness and metastasis [J].Cancer Research, 2015. 10.1158/0008-5472.

A new weapon against cancer and inflammation

NF-ΚB(nuclear factor-kappa B) is complex which consisted by a class of multigene family NF-κB-Rel. In vertebrates, it conclude 5 subunits: p105-p50(NF-κB1), p100-p52(NF-κB2), p65 (RelA), c-Rel and RelB. There are two major signaling pathway can active NF-ΚB (in picture 1).


The first is the classical pathway, NF-κB dimer and IκBα combined with its nuclear localization signal and DNA binding domain protein is inhibited by profilin of IκBα. Bacterial and viral infections as well as some of the ligand (TNF, IL-1, LSP, CD40L) can bind with corresponding receptors on the cells surface. Ligand bound receptor proteins can be raised to some joints receptor cytoplasmic side of the structure domain, which is capable of recruiting Iκ adapter protein kinase (IκK) binding complexes therewith. Then active IκK composite phosphorylate residue of two conserved serine of IκB. IκB is phosphorylated after will be ubiquitinated, the ultimate degradation by the 26S proteasome. The released NF-κB into the nucleus acts on the target gene.

In passing through the bypass, the binding of signaling molecules with the receptor induced NF-κB activation kinase NIK. Avtived NIK phosphorylate IκKα, and activated IκKα composite will phosphorylate P100. Phosphorylation leading to partial hydrolysis of P100 by P100 into P52, its nuclear localization signals and DNA binding domain is exposed, with the composition of the composite body into the nucleus RelB activate the site.

NF-κB is almost always expressed in all cells in the face of trauma, hypoxia, physical and chemical irritation and other stress conditions, NF-κB activation and nuclear translocation of large quantities, through the induction of various cytokines, chemokines, adhesion molecules, transcription enzymes and antimicrobial peptides, the rapid activation of the immune response, and thus play a central role in the inflammatory response link. In the past decade, researchers have done a lot of in-depth study for the role of NF-κB in cancer mechanisms. Abnormal activation of NF-κB has found in many different stages of the tumor and its development. Therefore, if the small-molecule inhibitors can be reduced NF-κB activity, these diseases will have important therapeutic implications.

In the latest article, researchers report that confirmed a complex natural product ainsliadimer A is a potent inhibitor of NF-κB signaling pathway. Ainsliadimer A selectively binds IKKα / β of 46 conserved cysteine ​​residues, inhibit their activity by allosteric effectors, thereby inhibiting the classical and non-classical NF-κB signaling pathway. Notably, ainsliadimer A can induce a variety of cancer cell death and tumor growth inhibition in vivo as well as endotoxin-mediated inflammation.

These findings not only confirm ainsliadimer A are potent IKKα / β inhibitor, also indicates ainsliadimer A can be used as lead compounds for the development of the treatment of cancer and inflammatory diseases of the drug.