Authors: Martha Powell, Future Science Group
An international team of researchers have identified a pro-metastatic protein interaction in lung cancer cells. This interaction, which is mediated by the Golgi apparatus, could be a target for future therapies aiming to prevent the spread of the disease.
In this study, presented recently in The Journal of Clinical Investigation, the team identified the role of a key protein termed PAQR11, which is found in the Golgi apparatus. The researchers observed that high levels of this protein were correlated with epithelial-to-mesenchymal transition and shorter survival in human cancers. In addition, PAQR11 was found to be essential for tumor cell migration and metastasis in lung adenocarcinoma models.
The team demonstrated that increased expression of PAQR11 occurs when the Golgi apparatus is activated by the ectopic expression of ZEB1 – a protein previously linked to epithelial-to-mesenchymal transition in lung cancer.
In addition, the scientists demonstrated that this increase in PAQR11 caused alterations in the transport of secretory vesicles from the Golgi apparatus. The study indicated that changes in the trafficking of vesicles could lead to modifications on the cell surface; making it possible for the cell to detach, become mobile and potentially metastasize.
Targeting the cell migration process could potentially reduce tumor growth and prevent metastasis; therefore, inhibiting the interaction elucidated by this study might present a future therapy for preventing the spread of lung cancer.
Author Daniel Ungar (University of York, UK) concluded: “Now that we recognize this system, there is the potential to develop a drug that interferes with this communication and prevents the Golgi apparatus from facilitating the movement of the membrane sacks. The next stage of this study will be to look at how we target this process without interrupting normal cellular functions of non-cancerous cells.”
Sources: Tan X, Banerjee P, Guo HF et al. Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11. J Clin Invest. doi:10.1172/JCI88736 (2016) (Epub ahead of print); University of York press release