Researchers at Karolinska Institutet have identified a previously unknown mechanism that affects the ability of cancer cells to spread in the body. The study, published in EMBO Molecular Medicine, shows that a process called chaperone-mediated autophagy (CMA) may function as a natural defense mechanism against metastases.
Cancer remains one of the most common and deadliest diseases worldwide. Cancer cells can spread through the bloodstream and begin growing in other organs; these are known as metastases and represent a frequent and severe complication that often determines the seriousness of a tumour disease. Blocking cancer cells' ability to spread is a crucial strategy, yet there are currently few effective treatments for cancer metastasis.
Unexpected findings
The researchers, led by Dr Helin Norberg and Dr Erik Norberg , have long studied CMA, a process in which cells break down specific proteins. By removing the LAMP2A gene, which regulates CMA, they discovered that cancer cells lacking a functional CMA process grew faster and formed more metastases.
"This was an unexpected finding. Previously, CMA was believed to stimulate cancer growth, but our results suggest the opposite", says Dr Helin Norberg.
To confirm their discovery, the researchers analysed patient samples from lung cancer patients with brain metastases. The results showed that the metastases had significantly lower levels of LAMP2A compared to the primary tumours. Similar patterns were observed in metastases from 19 different organs.
Tumour spread and autophagy
Cancer cells can alter their identity through epithelial-mesenchymal transition (EMT), a process that enhances their ability to spread. The researchers demonstrated that several proteins involved in EMT are broken down via CMA, indicating that CMA functions as a natural tumour-suppressing mechanism.
"A deeper understanding of metastasis-driving proteins can help us comprehend how cancer cells spread and develop new treatment strategies", says Dr Erik Norberg.
The current goal is to identify ways to activate CMA in order to prevent or eliminate metastases. The researchers are already well advanced in this field and hope that their discovery will pave the way for new treatment methods to combat cancer spread.
Many types of cancer lead to metastases, and today, one in three cancer patients already has metastases at the time of diagnosis. Gaining deeper insight into how metastasis-driving proteins can be eliminated in cancer cells could improve our understanding of the underlying causes of cancer cell spread.
"Our hope is that the new knowledge we have contributed will be utilised to develop effective treatments to prevent or eliminate metastases. This requires the activation of CMA - a research focus that we are fully committed to and have already made significant progress in"., says Dr Erik Norberg.
"This study is an excellent example of strong collaboration between clinicians and preclinical researchers from four different departments at Karolinska Institutet", he adds.
