Hexosamine Biosynthetic Pathway Positively Regulates Glutaminolysis Via SCA10 In NSCLC

Glycometabolism and glutaminolysis were the two primary carbon sources and nitrogen sources for NSCLC, which were rearranged compared with normal cells. It was reported that hexosamine biosynthetic pathway(HBP) is highly activated in NSCLC cells which are also addicted to glutamine. HBP and glutamine play significant roles in the development and progression of NSCLC, but the precise mechanism is not clear. Based on these, we used GAC as a bait to screen the interactors using the yeast two-hybrid system. One of them was Spinocerbellar Ataxin type 10(SCA10), which may be as an adaptor protein recruited OGT and GAC. Biochemistry experiments were showed that OGT could stabilized GAC protein. Thus, a novel metabolic pathway was found in NSCLC that HBP activates OGT to stabilize GAC with the help of adaptor protein SCA10, positively regulate glutaminolysis.We demonstrated that SCA10 couples glycometabolism to glutaminolysis for the first time. Therefore, The SCA10 may be a novel drug target for clinical therapy of NSCLC.