Already known for being an intracellular mediator, the SRC protein actually plays a bigger role: it also controls the production of the exosomes that cancer cells excrete into their environment. A discovery which can lead to new therapeutic avenues!
How do tumor cells function and communicate with each other and their environment? This is an important question if we are to continue to develop better-targeted and more effective cancer treatments. We do know that SRC, a protein physiologically involved in the regulation of intracellular signals, can demonstrate pro-oncogenic behavior in the event of deregulation. We also know that tumor cells have the ability to communicate with their environment via exosomes. These vesicles, which are loaded with enzymes, mediators, nucleic acids and more, are formed inside the cells and then transported into the intercellular space. They promote tumor progression and the formation of metastases.
For the first time, scientists from the Cancer Research Center of Marseille (CRCM) have recently identified a link between these two mechanisms. In fact, the SRC protein also controls the production of exosomes by the tumor cell. So, the key role of the SRC protein is both intracellular and extracellular, representing a potential target for future therapeutic developments.
Du mécanisme fondamental aux perspectives cliniques
For several decades, molecular biologists have attempted to elucidate the innumerable mechanisms governing cell functioning and interaction. Fundamental research teams, including Pascale Zimmermann's* at the CRCM, are working to gradually identify the thousands of mediators, proteins, receptors and interactions involved in the organization and communication of our cells. By deciphering physiological functioning, it is possible to identify the reasons for their dysfunction and, as such, determine potential therapeutic avenues early on.
This is the approach taken by the researcher and her team - by analyzing all the molecular mechanisms involving the SRC protein: "SRC is an enzyme of the kinase group that activates intracellular signals by chemically modifying certain mediators," she points out. In this research, performed in vitro on a breast tumor cell model, SRC has also been seen to be able to control the communication of the cell with its environment by interacting with the production of exosomes. For this, it uses another protein, known as syntenin, which is essential for the formation and loading of exosomes within the cell before they are released.
The prospects are enticing: "Acting on SRC or syntenin at the cellular level could limit the production of exosomes which, while enabling communication with their neighbors, are also involved in long-distance communication with other sites in the body. Inhibitors of SRC or syntenin could therefore theoretically limit tumor progression and dissemination." In the meantime, the team is continuing its research. "Now we're seeking to elucidate how exosomes form and understand how they govern communication between healthy and diseased cells."
*Unit 1068 Inserm/Aix-Marseille Université/CLCC, Spatio-Temporal Regulation of Cell Signaling team, Cancer Research Center of Marseille, Paoli-Calmettes Institute, Marseille
Imjeti NS et coll. Syntenin mediates SRC function in exosomal cell to cell communication. PNAS 2017 114 (47) 12495-12500; Publié en ligne le 6 novembre 2017. doi:10.1073/pnas.1713433114