Role for Oxoglutarate Carrier in Formation of Lung Cancer
Posted: Friday, April 5, 2019
Mitochondrial ATP production in non–small cell lung cancer (NSCLC) and melanoma seems to be dependent on SLC25A11, one of two antiporters in the malate-aspartate shuttle, according to Soo-Youl Kim, PhD, of the National Cancer Center, Goyang, Republic of Korea, and colleagues. Unchecked proliferation in cancer metabolism has long been known to depend on excess ATP. Through a series of in vitro and in vivo experiments, Dr. Kim and colleagues found that a main source of ATP in cancer cells was derived from the electron transport chain using cytosolic nicotinamide adenine dinucleotide plus hydrogen, a process dependent on the oxoglutarate carrier SLC25A11. Study results were published in EBioMedicine.
In this study, cell lines, mouse models, and tissue arrays from patients with NSCLC were used to test the role of SLC25A11 in cancer metabolism. In total, nine NSCLC cell lines were used: A549, H1650, EKVX, HOP62, H322M, H522, H1975, H23, and H226.
Compared with normal lung fibroblast (IMR90) cells, treatment using siRNA against SLC25A11 in A549 cells increased cell death by up to 400% over 72 hours. Knockdown of SLC25A11 using shRNA in A549 and H226 cells inoculated into mice resulted in tumor sizes about 80% smaller than controls. In KRAS-LA2 mice heterozygous for loss of SLC25A11, compared with controls, the tumor area and number of tumors were decreased by 46% and 40%, respectively. Lastly, staining in tissue samples from patients with NSCLC showed stronger SLC25A11 expression compared with normal lung tissue.
“Blocking SLC25A11 may have an advantage in stopping cancer growth by reducing ATP production,” concluded the authors. “The mechanisms underlying the regulation of SLC25A11 expression as well as the role of SLC25A11 in various cancers remain to be elucidated.”
Disclosure: The study authors reported no conflicts of interest.