A joint team of scientists, from University of Science and Technology of China and High Magnetic Field Laboratory, Chinese Academy of Sciences, identified that Polo-like kinase 1 (Plk1) plays a critical role for biosynthesis in cancer cells through activating pentose phosphate pathway (PPP).

Two hallmarks for cancer cells are the accelerated cell cycle progression as well as the altered metabolism, however, how these changes are coordinated to optimize the growth advantage for cancer cells are still poorly understood.

It has been established that Plk1 plays a critical role in various aspects of mitotic events, such as mitotic entry, centrosome maturation, and mitotic spindle assembly. Increasing evidence suggests that Plk1 is also involved in other cellular events in addition to mitosis.

While these significant observations accumulated over past years greatly extended the functions of Plk1 in facilitating human malignancies, up to date, there is no evidence to show that Plk1 is directly involved in biosynthesis or metabolic regulation.

Specifically, no metabolic enzymes have been identified so far as a direct target of Plk1, at least to the best of our knowledge.

The research team finds that Plk1 interacts with and directly phosphorylates glucose-6-phosphate dehydrogenase (G6PD), a rate-limiting enzyme of PPP.

By activating G6PD through promoting the formation of its active dimer, Plk1 increases PPP flux and directs glucose to the production of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) and ribose for the synthesis of macromolecules.

Importantly, they further demonstrate that Plk1-mediated activation of G6PD is indispensable for its role to promote cell cycle progression and cancer cell growth both in vitro and in vivo.

Collectively, these findings establish a critical role for Plk1 in regulating biosynthesis in cancer cells, exemplifying how cell cycle progression and metabolic reprogramming are coordinated for cancer progression.