A new study published in Science has uncovered a key mechanism underlying the control of a co-factor that is essential for all cells to grow and divide, and which may also play a key role in cancer cell growth.
Issam Ben-Sahra, PhD, assistant professor of Biochemistry and Molecular Genetics, was a co-author of the study.
It has long been known that all growing cells must continuously generate certain molecules that are precursors to larger and more complex macromolecules, and that this process depends on growth signals from outside the cell, which are relayed to cellular pathways and co-factors inside the cell.
In the current study, the scientists were able to demonstrate that a key signaling pathway, the Phosphoinositide 3-kinase/Akt (PI3K-Akt) pathway, is a critical part of the “master regulator” of cellular metabolism, linking growth signals from outside cells to the synthesis of the major molecules essential for cells to build more of themselves.
In particular, the investigators showed that the pathway displays a newly-discovered function in growing cells, especially cancer cells: combining the creation of molecules required for growth and division and supplying the increased energy a cell requires to sustain its growth.
The scientists uncovered new mechanisms by which growth signals, relayed through the PI3K-Akt pathway, control the synthesis of one critical co-factor, Nicotinamide Adenine Dinucleotide Phosphate (NADP), itself essential for all cell homeostasis and division.
The current study is important, the authors note, because it shows that the PI3K-Akt pathway displays a previously unknown function in all growing cells — but especially cancer cells: coupling biosynthetic reactions with the release of energy required to power cellular reactions.
According to the study, this process is facilitated by a key metabolic enzyme called NAD kinase (NADK), which converts NAD to NADP. Previous research established that elevated PI3K-Akt signaling is a common feature of many cancer cells.
Therefore, the authors note, the study suggests that uncontrolled PI3K-Akt signaling contributes to the unrestrained growth of cancer cells, by making available more energy for cells to grow and divide.
The study was the result of a collaboration with Brendan Manning, PhD, the corresponding author, and Gerta Hoxhaj, PhD, the first author of this study, both at Harvard T.H. Chan School of Public Health, and with long-standing support from Peng Gao, PhD, research assistant professor of Medicine in the Division of Hematology and Oncology and the operation director of the Metabolomics Developing Core at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Ben-Sahra and Gao are both members of the Lurie Cancer Center.
