Cancer: study unveils the molecular structure of LH3, the enzyme involved in metastases
An important milestone in the development of new drugs for the treatment of metastases associated with various forms of cancer has been reached by an Italian research team at the University of Pavia.
In a study published in Nature Communications, researchers unveiled the three-dimensional structure of LH3, an enzyme involved in metastases and in some rare genetic diseases involving collagen formation, such as Osteogenesis Imperfecta and Ehlers-Danlos and Bruck syndromes.
The research was carried out with the support of Armenise-Harvard and Cariplo foundations, AIRC-Italian Association for Cancer Research and with the support of MIUR- Ministry of Education, University and Research through the Departments of Excellence funding programme, as well as a Marie Curie fellowship awarded by the European Commission to Antonella Chiapparino.
Collagen is the most abundant protein in the human body which supports cells and tissues and its formation is due to the LH3 enzyme, belonging to the lysyl hydroxylase (LH) family of enzymes. The new study unveiled for the first time the three-dimensional structure at the atomic level of LH3, obtained using X-ray crystallography.
“Despite being known for over 40 years, until now not much was known about LH3 function” said Federico Forneris (pictured) of University of Pavia, who led the study. “This study is an important step forward in our study of genetic disorders of collagen: after the advances in the understanding of the molecular basis of ARC syndrome, published previously, we focused on the function of this enzyme, obtaining an important result that clarifies the mechanisms underlying some rare genetic diseases”, concluded Forneris.
Recent studies have also associated malfunctions in LH enzymes with the progression and formation of metastases in various types of solid tumours, because ‘collagen highways’ promoting cancer cell migration seem to form around cancer cells. “Our discovery is a major boost for the future development of drugs capable of preventing the formation of metastases”, said Luigi Scietti, lead author of the study.