Regulation of nutrient uptake controls cancer cell growth and metabolism
Solid tumours activate angiogenic signals to ensure an adequate blood supply. In parallel, amino acid transporters on the cell surface are also increased so as to provide nutrients for the higher metabolic and growth demands of cancers. We are studying a number of amino acid transporters, including L-type amino acid transporters (LAT1 and LAT3) and alanine-serine-cysteine transporter 2 (ASCT2) that mediate uptake of essential amino acids including leucine and glutamine. Leucine and glutamine are critical for the activity of mTORC1, which regulates protein translation and cell growth, as well as contributing to cellular energy and as carbon and nitrogen donors. We utilise a variety of in vitro and in vivo techniques to dissect out how these transporters are regulated, the pathways they modulate, and use high throughput drug screening to develop novel inhibitors as putative therapeutics.Our work has shown that cancer cells respond to the demand for amino acids through integrated developmental and stress-mediated pathways, leading to increased amino acid transporter expression and cell growth. Furthermore, ASCT2, LAT3 and LAT1 may provide novel therapeutic targets in early and late stage prostate cancer as well as other solid tumours such as melanoma and breast cancer.
About the speaker
Associate Professor Jeff Holst is a National Breast Cancer Foundation Fellow and Faculty Member leading the Origins of Cancer Program at the Centenary Institute in Sydney. His laboratory is focussed on understanding how amino acid transporters are regulated in cancer (Cancer Res 2011), how they contribute to prostate cancer development (J Path 2015) and metastasis (JNCI 2013), melanoma cell growth (IJC 2014) and more recently triple-negative breast cancer. His lab is also focussed on developing new therapeutics to target these transporters using in silico and natural compound screening approaches (ACS CB 2014; J Nat Prod 2015).
Time: 12:00pm - 1:00pm