A43
Members of the Proton-Assisted Amino Acid Transporter (PAT/SLC36) family regulate growth in human cancer cell lines
Shubana Kazi, Deborah Smith, David Meredith, Clive Wilson, C.A. Richard Boyd, Deborah C.I. Goberdhan
Oxford University, Oxford, UK
The PI3K/Akt pathway is now known to play a pivotal role in both normal and tumorigenic growth. Work in flies has played a key role in linking PI3K/Akt signalling to the more ancient nutrient-sensing cascade TOR (Target of Rapamycin) kinase, opening up the possibility that modulating local nutrient-sensing mechanisms might affect a broad range of cancers.
We have recently highlighted the Proton-Assisted Amino-acid Transporter (PAT or SLC36) family as potent regulators of IIS/TOR-mediated growth using an in vivo genetic screen in flies and shown that the growth-promoting properties of the PATs are strongly enhanced when PI3K/Akt signalling is increased. Since human PATs can substitute for Drosophila PATs, this suggests that the PATs may play an increasingly important role in promoting growth in tumour cells that upregulate PI3K/Akt. However, this role is yet to be tested in human cells.
We have started to analyse the growth-promoting effects of the PAT transporters in human cell culture using siRNA approaches. We find that two of the four human PATs, PAT1 and PAT4 are expressed at moderate to high levels in all or most cancer cell lines. Knockdown of either PAT1 or PAT4 strongly inhibits growth of multiple cancer cell lines derived from tissues including cervix, lung and breast. Blocking PAT function could therefore provide a novel route for suppressing the effects of excess signalling by the PI3K/Akt pathway that are commonly observed in human tumours.
