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A new paper by Pietilä et al. in Nature Communications, coauthored by Olav Andersen in collaboration with the group of Johanna Ivaska from Turku Bioscience Centre, identified a novel oncogenic function for SORLA that is best known for its association with Alzheimer’s disease.
2019.06.03 |
Fig. 7. Schematic illustrating the role of SORLA in the oncogenic fitness of HER2 in cancer cells.
So far, SORLA has mainly been studied in neurons where it acts as a sorting receptor for a precursor protein that when sorted in the absence of SORLA leads to Amyloid plaques – the pathological hall mark in brains of patients with Alzheimer’s disease. This goes along with recent findings that inactivating mutations in SORLA are strongly associated with the development of Alzheimer’s disease.
The new study focused on the role of SORLA in cancer cells, and found that here it regulates the oncogenic fitness of HER2. This protein is a strong driver of tumour growth, and is involved in about 20% of breast cancers as well as commonly found in bladder and gastric cancers. Here, SORLA promotes the recycling of HER2 back to the plasma membrane where it is active and drives the proliferation of cancer cells. When SORLA was removed from cancer cells, HER2 also became inactive and no longer able to drive tumour growth.
Previous studies have noticed such inverse correlation between Alzheimer’s disease and cancer. Even though both diseases are common among the aging population, it has been demonstrated that patients with Alzheimer’s disease have a lower risk to get cancer during their lives, and vice versa, cancer survivors have a lower risk to develop Alzheimer’s disease. So far no clear reason has been found to explain for this phenomenon, but the new study now suggests that SORLA may be one of the factors behind this inverse correlation.
Link: https://www.nature.com/articles/s41467-019-10275-0