Baylor College. US: A steroid receptor coactivator (SRC-2) drives the metabolic mechanism
that allows prostate cancer not only to grow but also to spread or
metastasize, said researchers at Baylor College of Medicine in a report
that appears online in the Journal of Clinical Investigation.
“This finding helps define a pathway against which we might develop a drug,” said Dr. Bert O’Malley,
chair of molecular and cellular biology at Baylor. “That would be
valuable against prostate cancer metastasis, which is the deadly
complication.”
SRC-2 is present in high levels and is particularly active in more
than one-third of metastatic prostate tumors. To encourage spread, it
reprograms the metabolism of an amino acid known as glutamine. SRC-2 is
activated by nutrient signaling by glutamine via mTORC-1-phosporylation.
(Phosphorylation turns genes on.) SRC-2 thus triggers
glutamine-dependent generation of new fat cells that promote the
survival and source of energy required for the spread or metastasis of
prostate cancer cells.
“When human prostate tumors were profiled metabolically, a massive
increase in the SRC-2 driven metabolic signature was identified in
metastatic cells compared to such signatures in localized tumors,” said
O’Malley.
Inhibiting SRC-2 genetically reduces survival and growth of
metastatic prostate cancer cells, which indicates that the newly
identified pathway could be a basis for future treatment.
Others who took part in this work include: Subhamoy Dasgupta,
Nagireddy Putluri, Weiwen Long, Bin Zhang, Jianghua Wang, Akash K.
Kaushik, Salil K. Bhowmik, Erin Stashi, Kimal Rajapakshe, Nicholas
Mitsiades, Cristian Coarfa and Arun Sreekumar, all of Baylor; Michael
M. Ittmann of Baylor and the Michael E. DeBakey Veterans Affairs Medical
Center and Arul M. Chinnaiyan and Christine A. Brennan, both of Ann
Arbor, Michigan.
Funding for this work came from the Alkek Center Metabolic Core, the
Challenge Award from Prostate Cancer Foundation (B.W.O), The National
Institutes of Health and National Institute of Diabetes and Digestive
and Kidney Diseases (Grant 5P01DK059820 (B.W.O), Cancer Prevention
Research Institute of Texas (CPRIT) [Grant) RP100348 (B.W.O),
CPRIT-MIRA-RP101251-P02 (B.W.O), CPRIT- RPN120092, 1R01CA133458 (A.S)
and 1U01CA167234 (A.S)].
O’Malley holds the Thomas C. Thompson Chair in Cell Biology.