New anti-cancer target in enzyme MAP4K3

Mar 14 2007

Scientists working at the Institute for Cancer Research have found a new anti-cancer target in MAP4K3, an enzyme which is able to 'switch on' the growth-promoter mTOR.

MAP4K3 is one of the mitogen-activated protein (MAP) kinases: serine/threonine-specific protein kinases that respond to extracellular stimuli (mitogens) and regulate various cellular activities, such as gene expression, mitosis, differentiation, cell survival and apoptosis.

mTOR (mammalian target of rapamycin) is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. It combines input from multiple upstream pathways, including insulin, growth factors and mitogens while functioning as a sensor of cellular nutrient and energy levels and redox status. Its malfunction is implicated in various human diseases, especially types of cancer.

The paper, by Greg Findlay, Lijun Yan, Julia Procter, Virginie Mieulet and Richard Lamb is published in the Biochemical Journal and is now available with an associated commentary. It reveals that MAP4K3 plays an important part in mTOR function and could be a target for drug intervention in tumour growth.

Professor George Banting, Chair of the Editorial Board, said "The importance of this paper is that we now have a 'way in' to the mTOR signalling pathway which is regulated by amino acids, but not by growth factors, such as insulin/IGF1. Inhibitors of MAP4K3 should switch off mTOR and so inhibit cell growth and proliferation. This is very exciting."