Breakthrough in cell signaling may enable smarter cancer drug design
Baku, May 14, AZERTAC
Scientists have uncovered a previously unknown communication mechanism between cells that may help explain why some cancer treatments have been less effective than expected, TPS-IL reported citing the University of Haifa.
The study, published in the peer-reviewed Nature Communications, focuses on the Notch receptor, a highly conserved signaling molecule involved in how cells send and receive developmental and regulatory instructions, including in cancer-related processes. Until now, scientists believed Notch primarily functioned as a receptor that receives signals from other cells on the cell surface.
However, the Israeli research suggests the receptor has an additional role. In certain contexts, Notch may also participate in “reverse signaling,” influencing neighboring cells directly. This outward communication can trigger nearby cells to engulf living cells in a process known as phagoptosis. This mechanism is typically associated with the removal of dead or damaged cells, rather than healthy ones.
“It is possible that the new mechanism we have found could help explain why treatments that focus only on internal signaling within cells have not led to noticeable results so far, since the Notch receptor may also influence neighboring cells,” said Prof. Hila Toledano, one of the study’s authors.
The research was led by doctoral students Heba Abu Rumi and Nivin Sarhan in Toledano’s laboratory in the university’s Department of Human Biology.
Cells communicate continuously through molecular signals, enabling tissues to grow, repair, and function properly. The Notch pathway has long been recognized as one of the central regulators of this system, and disruptions in its activity have been linked to cancer and various genetic disorders.
To investigate whether Notch has additional roles beyond its established function, the researchers used the fruit fly Drosophila melanogaster as a model organism. They tracked cellular behavior using live imaging, fluorescent markers, and targeted genetic modifications.
The results challenge the standard model of Notch signaling. The receptor was found to interact directly with a different receptor in neighboring cells called Draper, which is involved in cellular clearance and debris removal. This interaction triggered neighboring cells to engulf living cells, effectively removing them from tissue.
Importantly, this effect occurred independently of Notch’s well-known internal signaling pathway. Even when internal signaling was experimentally disabled, the outward signaling effect remained. This indicates that Notch has two distinct functional modes: one operating within the cell and another influencing adjacent cells through direct interaction.
The study also found a clear correlation between Notch levels and cell elimination: higher levels of Notch increased the rate of cell engulfment, while reduced levels decreased it. When the Draper receptor was removed, the process was completely blocked, confirming its essential role in the mechanism.
The researchers say these findings may prompt a reassessment of how Notch-related diseases are studied, including certain cancers. Many experimental therapies have focused primarily on blocking internal signaling pathways within affected cells. The findings may open the door to therapies that reprogram surrounding cells to recognize and remove cancer cells more effectively.
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