PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a “pseudokinase”, has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2−/− mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.
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MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression by translational repression or
deregulating of messenger RNAs. Accumulating evidence suggests miRNAs play various roles in the development and progression of
lung cancers. Although their precise roles in targeted cancer therapy are currently unclear, miRNAs have been shown to affect the
sensitivity of tumors to anticancer drugs. A large number of recent studies have demonstrated that some anticancer drugs exerted antitumor activities by affecting the expression of miRNAs and their targeted genes. These studies have elucidated the specific biological
mechanism of drugs in tumor suppression, which provides a new idea or basis for their clinical application. In this review, we summarized the therapeutic mechanisms of drugs in lung cancer therapy through their effects on miRNAs and their targeted genes, which
highlights the roles of miRNAs as targets in lung cancer therapy.
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