Novel insights of how prostate cancer causes secondary tumors

September 03, 2020

An increased awareness on a molecular level of what mechanisms prostate cancer cells use to become mobile and start spreading may in the long run provide new opportunities for treatment of aggressive prostate cancer. This according to a new study by researchers at Umeå University, Sweden, in collaboration with researchers in Uppsala and Tokyo.

"We can show that one specific amino acid in a signalling molecule plays an important role in mobilising the cancer cells and in that way increase the risk of metastases," says Professor Maréne Landström, Umeå University.

This research has studied the growth factor TGF-β, Transforming Growth Factor Beta, which regulates how cells grow and specialise. Previous studies have shown an overproduction of TGF-β in many cancer forms, one being prostate cancer. High levels of TGF-β have proven to be strongly linked with poor prognosis and low survival rates as a consequence of the growth factor stimulating cancer cells to spread in the human body and cause life-threatening secondary tumors - so-called metastases.

TGF-β regulates the expression of the protein Smad7 - an active component in the TGF-β signalling chain. In healthy cells, Smad7 can prevent continued TGF-β signalling via negative feedback. However, Maréne Landström and her research group and colleagues can now show, contrary to previous belief, that, in cancer cells, Smad7 can reinforce the development of tumors by regulating the gene expression of HDAC6 and c-Jun.

The specific amino acid that has caught the researchers' attention is called Lys102 and is found in Smad7. This amino acid binds to particular gene-regulating functions in DNA to increase production of the gene expression HDAC6 and c-Jun. This has the effect that cancer cells become more mobile and more prone to form metastases. Researchers have been able to see a clear connection between all these variables and a negative prognosis for prostate cancer.

"The good news is that by using treatment with an HDAC6 inhibitor, we can make prostate cancer cells lose their mobility. In that way, novel opportunities can open up for treatments that reduce the risk of metastases," says Maréne Landström.

Clinical trials are now taking place in the UK to find specific HDAC6 inhibitors in patients with solid tumors, which means that treatments using HDAC6 inhibitors can become a complement in the cancer treatment of patients with hard-to-treat forms of disease. Future studies can explore the benefit of indicating expressions of Smad7, HDAC6 and c-Jun to enable new and more specific treatments for men with aggressive prostate cancer.

The study also shows an entirely new function of Smad7 in the way that it can recruit Smad2 and Smad3 to the place of transcription for these genes. Previously, it has been thought that Smad7 held the role of inhibitor for TGF beta-Smad2/3 transcriptional activity.
-end-


Umea University

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.