Vasileios Papalazarou, James Drew and Beatson colleagues made a pre-print available that lends further evidence towards the idea that cancer cell behaviour can be influenced by sensing mechanical cues from the environment. Notably, pancreatic cancer cells, in response to a softer culture substrate, reprogrammed their gene expression, releasing factors to alter their own surroundings. In particular, the scientists found that the upregulation of collagen-VI and changes to the extracellular matrix ultimately encouraged the migration and invasion of these cells.
In their article in Developmental Cell, Kai Cao, Joel Riley and co-authors reported a link between impaired mitochondrial function and DNA damage. Dysfunctional, fragmented mitochondria engaged in a process called minority MOMP that triggers the activity of caspases which in turn leads to oncogenic DNA damage. They also suggested mechanisms by which a protein called BCL-2 could be targeted to prevent these cancer promoting signals.
In a multi-omics approach in iScience, Mark Salji, Hing Leung and others uncovered targetable pathways in models of castration-resistant prostate cancer (CRPC). Untargeted metabolomics revealed an accumulation of NAA and NAAG across different models of CRPC. Although additional work is required to evaluate the highlighted pathways, this study demonstrated the feasibility of a multi-omics approach for providing a data-rich resource for cancer research.
A study published in Cell Death & Differentiation by Tim Humpton together with Beatson scientists described a role for p53 in supporting the repair and recovery from acute liver damage. Through involvement of the detoxifying enzyme Cyp2a5/CYP2A6, p53 limited cell stress induced by reactive oxygen species and mediated regenerative processes – a function of p53 that also prevailed during chronic liver injury. As such, the authors suggested further investigation into Cyp2a5/CYP2A6 as a prognostic marker.
Today the MRC National Mouse Genetics Network is announcing a multi-million pound backing of mouse genetics for disease modelling. It will capitalise on the UK's international excellence in the biomedical sciences, creating 7 challenge-led research clusters.
The Network brings together experts from across the UK. The Mary Lyon Centre at MRC Harwell will act as the central hub of the Network, sharing access to specialist facilities, resources, data, and training with all other Network members. The partnerships established by the Network will enable integration of basic science research with clinical findings in order to accelerate our understanding of human disease and translation to patient benefit.
Prof Owen Sansom, Network Director & Director of the CRUK Beatson Institute:
"We're excited to announce this first set of research clusters forming the MRC National Mouse Genetics Network and to synergising our efforts to deliver impactful preclinical science through comprehensive sharing of data, resources, and expertise."
Dr Seth Coffelt, Prof Jen Morton and Prof Daniel Murphy are members of the Cancer Cluster led by Prof Karen Blyth at the CRUK Beatson Institute/University of Glasgow and Prof Louis Chesler at The Institute of Cancer Research, London. The Cancer Cluster is receiving ~£2.9 million of MRC investment and aims to use complex state-of-the-art mouse models to improve the understanding and treatment of cancer. The next generation of modelling will better replicate the complexity of the disease and more accurately predict therapeutic outcomes through the use of deep molecular phenotyping and novel strategies for generation of sophisticated mouse models which reflect all stages of disease progression.
Prof Karen Blyth, Co-Lead Cancer Cluster MRC Mouse Genetics Network:
"We are delighted to be part of the MRC National Mouse Genetics Network and have a fantastic team of scientists and clinicians within our Cancer Cluster eager to collaborate with the network and harness the opportunities this affords us for accelerating cancer discoveries to benefit patients"
Scientists as the camerawomen and -men of the unknown is the motto of a recently founded educational project. Bringing together art and science, Cell Worlds now stages an immersive experience in Bordeaux, France of the microscopic world of the human body – told through state-of-the-art fluorescent images by expert scientists like Dr Anh Hoang Le and Prof Laura Machesky at the Beatson.
Opening Event at the Cell Immersion exhibition in Bordeaux, France; right-hand installation shows work on melanoma cell migration by Anh Hoang Le Image Credit: Bertrand Bernager and Cell Worlds
One of the biggest showcases of scientific images, Cell Worlds brings together the works of 25 teams from world-renowned research institutes around the globe. Their aim - to awe the public with the beauty of, but also to introduce them to the complexity of life at cellular level. In a documentary style, their first project Cell Immersion features imagery of real live cells and explores how these single units of life move, hunt, divide and transmit information.
Prof Laura Machesky:
"I was delighted to be asked to contribute to Cell Worlds, along with Anh Hoang Le, whose beautiful microscope images attracted their attention. This is a real chance to communicate more broadly about the beauty of the cell as the most basic unit of life. It also highlights how rapidly our knowledge of biomedicine is advancing through technological breakthroughs in imaging."
Dr Anh Hoang Le and Prof Laura Machesky study the migration, invasion and metastasis of cancer cells and in particular how the proteins CYRI-A and CYRI-B influence the cells' ability to spread to distant sites. Within Cells Worlds you can follow their footage of two melanoma cell lines - one more invasive and one less invasive- mixed together, but migrating at different speeds; showing the aggressiveness of cancer cell migration.
The Cell Immersion installation can be visited in Bordeaux until the 2nd January 2023, but if you can't make it to France, maybe you can you spot some more of Anh's images in the documentary on YouTube?
Le AH, Yelland T, Paul NR, Fort L, Nikolaou S, Ismail S, Machesky LM. CYRI-A limits invasive migration through macropinosome formation and integrin uptake regulation. J Cell Biol. 2021;220.
Yelland T, Le AH, Nikolaou S, Insall R, Machesky L, Ismail S. Structural Basis of CYRI-B Direct Competition with Scar/WAVE Complex for Rac1. Structure. 2021;29(3):226-237.e224.
We would like to extend a warm welcome to Dr Tom MacVicar, who recently took up a junior group leader position at the Beatson. Tom has joined us from the Max Planck Institute for Biology of Ageing in Cologne to establish his first independent research group here in Glasgow.
Mitochondria form the focus of work in Tom's lab. The group's goal is to understand the mitochondrial changes - in form, function and make-up – that occur during cancer development. The lab will pursue the identification of mitochondrial metabolite transporters and investigate how they aid rewired metabolic demands in support of cancer cell proliferation. Further research will concentrate on the possible translation of these findings into interventional cancer therapeutics.
"I'm delighted to join the Beatson where my team will help drive the discovery and understanding of metabolic vulnerabilities in cancer. Cancer metabolism is a key research theme at the Institute and I'm excited to interact with, and learn from, world-class cancer research groups at the Beatson and University of Glasgow. Our work will also depend on close collaboration with the fantastic research facilities available here."
We are also looking forward to the arrival of Prof Vicky Cowling, who will join the Institute in May. Vicky is relocating her research group to Glasgow from the Centre of Gene Regulation and Expression, University of Dundee.
The Vicky's lab aims to understand how gene expression is regulated in health and disease. In particular, the team is interested in the RNA cap – a structure found on RNAs that not only protects RNA but is also involved in its processing. The group's research investigates RNA cap biochemistry and regulation in development, immune cell activation and following oncogene dysregulation in cancer.
"We are delighted to be moving to the Beatson and becoming part of this vibrant and collaborative community of scientists. Researchers at the Institute are dedicated to making discoveries in human biology and advances in cancer research – we look forward to joining this effort."
In the Journal of Medicinal Chemistry, Tamas Yelland and Esther Garcia presented a novel, alternative KRAS targeting strategy - tagging it for relocation to the cytoplasm. While sustaining KRAS binding to the protein PDE6D, KRAS moved away from its usual site of action at the cell membrane, leading to reduced downstream KRAS-oncogenic signalling. As the levels of the two proteins naturally vary between cell types, further study is required to develop a KRAS:PDE6D stabiliser that could be used as a successful anti-cancer therapy.
Together with Beatson scientists, Tim Humpton (from the Vousden lab at the Francis Crick Institute) has described an easier way of tracking p53 activity. The study, published in Science Signaling, introduced a new near-infrared reporter that enables investigation of p53's role in health and disease without the need for further intervention. While confirming the role of p53 in the liver after irradiation or paracetamol treatment, further applications of the reporter will allow the study of p53 activity during tumour development, offering insights into when to attempt therapeutic intervention.
Dominik Koessinger, David Novo and colleagues made a pre-print available on bioRxiv that identified a cell communication tool involving p53-mutant glioblastoma cells releasing extracellular vesicles. Favouring the sorting of podocalyxin into these vesicles stimulated other brain cells to create an invasive environment and promoted cancer cell infiltration in the brain. This study highlighted potential druggable targets for a form of glioblastoma with a particularly poor prognosis.
In a collaborative effort led by Beatson scientists and the University of Newcastle, a pre-print on bioRxiv showed that inhibiting CXCR2 could sensitise liver cancer to immunotherapy when patients were also affected by non-alcoholic fatty liver disease. Mechanistically, the treatment switched tumour neutrophils to an anti-tumour phenotype and enhanced the response of other immune cells. This suggests anti-CXCR2 therapy might be a promising anti-cancer agent in patients with liver cancer.
SCOTS scientists are set to receive a major cash injection from Cancer Research UK.
Today (Friday, February 4), on World Cancer Day, the charity is announcing that experts at the Cancer Research UK Scotland Centre will receive around £12 million over the next five years for their ground-breaking work, as part of the development of a unique chain of cutting-edge research hubs around the UK.
This World Cancer Day also marks Cancer Research UK's 20th anniversary.
The £12 million will be used to accelerate work into diagnosing and treating cancers which are among the most prevalent in Scotland, including bowel cancer, mesothelioma, liver cancer and brain tumours.
Professor Ian Tomlinson, Co-Director of the Cancer Research UK Scotland Centre, said: "We've had a challenging year and COVID-19 has slowed us down. But we will not stop working hard to find new treatments for cancer, and this investment will give us the tools we need to deliver high quality research which will make the biggest difference for patients.
"This investment means we will be able to further develop our work in translational research – getting cutting edge discoveries from the laboratory to patients and learning as much as possible from patients to initiate new research."
Professor Owen Sansom, Co-Director of the Cancer Research UK Scotland Centre, added:
"The new Cancer Research UK Scotland Centre will bring some of the best scientists in Scotland together to tackle some of the biggest cancer challenges that matter to people across Scotland.
"We will have a relentless focus on tackling cancers which affect our fellow citizens, drawing on expertise built up over many decades.
The Scotland Centre, comprising scientists from Edinburgh and Glasgow, has been chosen as one of just seven locations to secure funding in the latest review of the Cancer Research UK Centres network of excellence. These are world-class research centres which draw together leading research and medical expertise to drive the best possible results for cancer patients.
Every year, 33,200 people are diagnosed with cancer in Scotland*.
The multimillion-pound investment in the nation's cancer research is welcomed by bowel cancer survivor Iain Kerr, 66, from Helensburgh, who last year celebrated the arrival of his first grandchild.
Dad-of-two Iain was diagnosed with bowel cancer in January 2014 – just three months after moving home to Scotland from southwest England to retire with wife Wendy.
Then aged 58, the move meant Iain was eligible for Scotland's bowel cancer screening programme, which led to the discovery of a tumour in his lower bowel.
A keen hillwalker, Iain says when he left Vale of Leven Hospital in shock after hearing his diagnosis, he looked to Ben Lomond in the distance and thought, "Will we ever walk up there again?"
But following surgery to remove his tumour and a bowel resection – which was carried out using a surgical procedure never before performed in Scotland – Iain was told he wouldn't need any further treatment.
Welcoming Cancer Research UK's £12 million investment in the Cancer Research UK Scotland Centre, he said: "As far as I'm concerned, research and screening saved my life. The specialist surgery I had – a procedure that was carried out in Scotland for the first time – that's down to research.
"If I had been diagnosed with cancer twenty years ago, the outcome might not have been the same for me. I'm so grateful for the treatment that saved my life. I've been given the greatest gift of all – more precious moments with my loved ones, including meeting my beautiful granddaughter, Jasleen."
Iain continued: "I was lucky enough to avoid chemotherapy, but not everyone is as fortunate as I was. It's fantastic news that Cancer Research UK is investing £12 million in this new research centre in Scotland and bringing together the country's top experts from Edinburgh and Glasgow. I hope that this new funding and collaboration will lead to better, kinder treatments for people with bowel cancer, and other cancers impacting the lives of people across Scotland."
Dr Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, said:
"This past year proves, more than any other, the value of investing in science and medical research, and what can be achieved with collective focus and collaboration. Just like science is our route out of the pandemic, science is our route to beating cancer.
"Despite the impact of the pandemic on the charity's income, we are funding some of the best and most promising research in Scotland to help more people survive.
"Survival rates have doubled since the early 1970s and Cancer Research UK's work has been at the heart of that progress. Every step our doctors, nurses and scientists take relies on every pound raised through fundraising, and they need your support now more than ever.
"Our determination to beat cancer hasn't faltered and we are even more focussed on our ambition of seeing 3 in 4 people survive their cancer by 2034. One in two of us will get cancer in our lifetimes, and all of us can support the research that will beat it."
Marked on February 4, World Cancer Day is an international initiative, uniting people across the globe to take action against the disease.
For Cancer Research UK the awareness day takes on extra significance this year, as it celebrates its 20th birthday.
While the charity was formed in 2002, its history dates back to the founding of the Imperial Cancer Research Fund in 1902. Its work has been at the heart of some of the biggest developments in cancer, from radiotherapy to some of the most used cancer drugs around the world today.
And now the cutting-edge research it funds has helped lead to more people than ever in the UK surviving their cancer for 10 years or more.
We also welcome the extended leadership team: Prof Gareth Inman - Chief Operating Officer (left), Dr Jackie Beesley - Centre Manager (middle), Prof Charlie Gourley - Clinical Lead (right)