Inhibition of ribosome biogenesis as a novel approach for multi-stage cancer treatment
Nearly ninety per cent of all cancer patient deaths are due to metastasis. A study from IGP shows that a process that allows the cells to metastasise is aided by the synthesis of new ribosomes, the cell components in which proteins are produced. The results open the possibility for new treatment strategies for advanced cancers. The study is published in Nature Communications.
As tumours progress towards advanced stages they dedifferentiate, become more aggressive and lose the characteristics of the origin tissue. They also acquire the migratory capacity that allows the tumour to spread or metastasize to distant sites in the body, eventually causing patient death.
For epithelial tumours to metastasis the tumour cells undergo a process known as the epithelial-to-mesenchymal transition (EMT), which allows the cells to develop migratory ability. During EMT, cells also lose their proliferative capacity and become more stem-like. This remarkable transition leads to both increased invasiveness and an ability to evade numerous cancer treatments including hormonal therapies.
In the present study the researchers found that EMT is aided by the synthesis of new ribosomes, which serve to synthesize the proteins required for cell functions. Their study therefore argues that ribosome biogenesis may be more than just a pro-proliferative process.
“Until recently, ribosomes have been considered to play only passive roles during the production of proteins. Our study shows that ribosomes potentially have complex, active roles and suggests that more attention should be given to understanding how ribosomes contribute to cell physiology in health and disease states,” says Theresa Vincent, group leader at the IGP, who has led the study together with Scott C. Blanchard at Weill Cornell Medicine, USA.
The researchers also demonstrated that by inhibiting the formation of new ribosomes, aggressive and hormone insensitive tumours could be partially reverted to a benign and non-metastatic type.
“We used a small molecule called CX-5461 to inhibit ribosome biogenesis in mouse models of human tumours. We found that primary tumours reverted from an invasive type to a non-invasive type as well as potentially regaining sensitivity to hormonal therapy. Importantly, CX-5461 treatment also resulted in a marked reduction of number lung metastases. This suggests that treatment with CX-5461 may enhance hormone therapy responsiveness in patients where this kind of treatment doesn’t work any more. We find this to be a remarkable breakthrough and we are currently pursuing a number of additional validation studies,” says Theresa Vincent.
The study was by performed by a multi-institutional group of scientists from Uppsala University, Karolinska Institutet and Lund University in Sweden, together with researchers in USA, Austria, Spain and United Arab Emirates.
Disrupted immune cell navigation in lymph nodes of breast cancer patients
Different types of breast cancer tumours differ in how they affect the function of the lymph nodes. In patients with invasive breast cancer, the vessels and supporting tissue of the lymph nodes are altered, which cannot be seen in patients with a non-invasive cancer called (ductal cancer in situ). This is shown in a new study from Maria Ulvmar’s group at IGP, published online in the scientific journal Cancers.
Oral contraceptive pills protect against ovarian and endometrial cancer
A comprehensive study from Uppsala University, involving more than 250,000 women, shows that oral contraceptive use protects against ovarian and endometrial cancer. The protective effect remains for several decades after discontinuing the use. The study is published in the journal Cancer Research.
Vener bakom blodkärlsmissbildningar i hjärnan
In the condition known as cavernoma, lesions arise in a cluster of blood vessels in the brain, spinal cord or retina. Researchers in Elisabetta Dejana's group at IGP can now show, at molecular level, that these changes originate in vein cells. This new knowledge of the condition creates potential for developing better therapies for patients. The study has been published in the journal eLife.
World’s largest ever DNA sequencing of Vikings
Genetic examinations of more than 400 Viking age skeletons reveal that the Vikings that raided Europe came from relatively isolated groups in Scandinavia and many of them had a genetic influx from Asia or Southern Europe. This is presented in a study in the journal Nature, in which Marie Allen and Magdalena Bus from IGP have participated.
Internet-based support can reduce depressions symptoms in cancer patients
The internet can be used to provide education and support for self-management interventions to alleviate depression symptoms in individuals with cancer. This is shown in a study from Birgitta Johansson’s group at IGP.
Leakage from blood and lymphatic vessels is differently regulated
Researchers from IGP show in a new study that cell signalling regulating vessel leakage differs between blood and lymphatic vessels. The findings suggest a possibility to modulate this signalling in order to selectively control lymphatic vessel function and to treat diseases characterised by lymphatic vessel leakage.
New early biomarker for several cancer diseases
In a study including more than 400 hospital patients with 18 different cancer diagnoses, researchers have been able to show that EVP, extracellular vesicles and particles, could be used as biomarkers for several cancer diseases. The study has been led by researchers from among others IGP.
New findings on enzymes with important role in SARS-CoV-2 infection
Researchers at IGP have described the presence, throughout the human body, of the enzyme ACE2. This is thought to be the key protein used by the SARS-CoV-2 virus for host cell entry and development of the disease COVID-19. In contrast to previous studies, the study shows that no or very little ACE2 protein is present in the normal respiratory system. The results are presented in Molecular Systems Biology.
Unexpected associations found between drug response and cell changes in brain cancer
Therapies for treating glioblastoma brain cancer can be delivered with greater precision and existing drugs can be used in new ways. These are the conclusions from a study from IGP investigating a large number of cell samples from patients with brain tumours. The researchers have characterised how changes in glioblastoma cells influence the effect of different drugs. Their findings are published in the journal Cell Reports.
New method to identify genes that can drive development of brain tumors
Researchers at Uppsala University have developed a method for identifying functional mutations and how these affect genes with significance for the development of glioblastoma – a malignant brain tumor with very poor prognosis. The study is published in Genome Biology.
New effective way to inhibit lymphatic malformations
Lymphatic malformation is a debilitating and often incurable disease. Taija Mäkinen’s research group has in an international collaboration studied cellular mechanisms leading to abnormal vessel growth and identified a combination therapy that may allow effective treatment of these malformations.
Lymphatic vessels in mice and humans: alike yet different
In an international collaboration, researchers from IGP have mapped the lymph node lymphatic vessels in mice and humans down to the level of individual cells. The results may eventually help scientists to discover new methods for strengthening the immune system against viruses and cancer. Their work has been published in the journal Frontiers of Cardiovascular Research.
Scientists identify cause of leakiness in eye diseases
Targeting a molecule that contributes to leaky eye vessels, while sparing nerve and blood-vessel cells, could be a safer treatment strategy for age and diabetes-related vision loss. Scientists at IGP have identified a key step in the process that leads to leaky vessels and harmful swelling in eye diseases, according to a new study published today in the journal eLife.
Changes in cellular degradation hubs can lead to cancer
Cancer cells grow and divide in an uncontrolled manner. A new study from IGP now shows how alterations in a cell’s degradation hubs, called lysosomes, can cause abnormal cell growth. The results are published today in the scientific journal Nature Communications.
Careless cancer cells may be susceptible to future drugs
Could the ability of cancer cells to quickly alter their genome be used as a weapon against malignant tumours? Researchers at IGP have succeeded in developing a substance that has demonstrated promising results in experiments on both animal models and human cancer cells. The study is published in the journal Nature Communications.
Smart algorithm finds possible future treatment for childhood cancer
Using a computer algorithm, scientists at IGP have identified a promising new treatment for neuroblastoma. This form of cancer in children, which occurs in specialised nerve cells in the sympathetic nervous system, may be life-threatening. In the long term the discovery, described in the latest issue of the scientific journal Nature Communications, may result in a new form of treatment for children in whom the disease is severe or at an advanced stage.