Protein Pumps Power Prostate Cancer Growth

Cancer researchers have traced the molecular pathway used by rapidly growing prostate cancer cells to maintain sufficient levels of the essential amino acid leucine.

Depriving cancer cells of required nutrients is a potential approach to treating the disease while causing minimal damage to normal cells and tissues. In the October 17, 2011, online edition of the journal Cancer Research investigators at the Centenary Institute (Sydney, Australia) reported that prostate cancer cells use protein pumps (L-type amino acid transporters) such as LAT1 and LAT3 to mediate the uptake of essential amino acids. These cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 (mammalian target of rapamycin) signaling and cell growth.

Inhibiting LAT function was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cell cultures. Results showed that these cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 (activating transcription factor 4) regulation of LAT1 expression after amino acid deprivation.

"This information allows us to target the pumps - and we have tried two routes," said senior author Dr. Jeff Holst, head of the origins of cancer group at the Centenary Institute. "We found that we could disrupt the uptake of leucine firstly by reducing the amount of the protein pumps, and secondly by introducing a drug that competes with leucine. Both approaches slowed cancer growth, in essence starving the cancer cells."

"We have a better understanding of the links between prostate cancer and eating foods high in leucine," said Dr. Holst. "Diets high in red meat and dairy are correlated with prostate cancer but still no one really understands why. We have already begun examining whether these pumps can explain the links between diet and prostate cancer."

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Centenary Institute