Mastl: Potential target for cancer treatment?
The project 'Role of the protein kinase Mastl in cell division and cancer' (MASTL CDC) described the physiological function of Mastl in mammals. This led to exploring its potential as a new target for cancer therapy. Most Mastl studies have been done with Drosophila or Xenopus extracts. Mastl indirectly inhibits Protein Phosphatase 2 A (PP2A) through the phosphorylation of its two inhibitors, Ensa and Arpp-19. During MASTL CDC the scientists generated the first genetic model of this enzyme in mammals. They discovered that cells lacking Mastl cannot divide properly. In other words, the absence of Mastl impairs cell proliferation. The antiproliferative function of Mastl opens the possibility to target it as a part of cancer therapy. The therapeutic advantage of Mastl is that it acts by blocking the tumour suppressor PP2A, and inhibition of Mastl could reactivate PP2A. PP2A is an important tumour suppressor that inhibits many oncogenic pathways involved in cancer progression. Project results showed that while elimination of Mastl in vivo in young mice compromised survival, adult mice were only mildly affected. This suggests low toxicity in future Mastl-based therapies. The project data also suggest a role for Mastl in DNA damage repair. Elimination of Mastl could be beneficial in DNA damage-based therapies. Finally, Mastl has potential as a prognostic factor for breast cancer, because high expression of Mastl correlates with poor prognosis in breast tumours. MASTL CDC confirmed Mastl/Greatwall as an important potential target for cancer treatment. Current efforts are directed at identifying the types of tumours that would respond to Mastl inhibition-based therapies. The project's findings significantly contribute to the development of novel targeted cancer therapies.
Keywords
Mastl, cancer, Greatwall, mitosis, DNA damage, cell division
