Abstract:
:Hexokinase-II (HK2) is a key enzyme involved in glycolysis, which is required for breast cancer progression. However, the underlying post-translational mechanisms of HK2 activity are poorly understood. Here, we showed that Proviral Insertion in Murine Lymphomas 2 (PIM2) directly bound to HK2 and phosphorylated HK2 on Thr473. Biochemical analyses demonstrated that phosphorylated HK2 Thr473 promoted its protein stability through the chaperone-mediated autophagy (CMA) pathway, and the levels of PIM2 and pThr473-HK2 proteins were positively correlated with each other in human breast cancer. Furthermore, phosphorylation of HK2 on Thr473 increased HK2 enzyme activity and glycolysis, and enhanced glucose starvation-induced autophagy. As a result, phosphorylated HK2 Thr473 promoted breast cancer cell growth in vitro and in vivo. Interestingly, PIM2 kinase inhibitor SMI-4a could abrogate the effects of phosphorylated HK2 Thr473 on paclitaxel resistance in vitro and in vivo. Taken together, our findings indicated that PIM2 was a novel regulator of HK2, and suggested a new strategy to treat breast cancer.
journal_name
Oncogenejournal_title
Oncogeneauthors
Yang T,Ren C,Qiao P,Han X,Wang L,Lv S,Sun Y,Liu Z,Du Y,Yu Zdoi
10.1038/s41388-018-0386-xsubject
Has Abstractpub_date
2018-11-01 00:00:00pages
5997-6009issue
45eissn
0950-9232issn
1476-5594pii
10.1038/s41388-018-0386-xjournal_volume
37pub_type
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