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.
MEDICA-tradefair.com; Source: Umeå University
