Abstract
Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2 partly accounted for interleukin-22-mediated cellular proliferation in DLD-1 cells. In vivo, our data demonstrated that interleukin-22 significantly promoted tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In summary, our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells.
Highlights
Colorectal cancer (CRC) ranks as the third most common cancer and the fourth leading cause of death in the world [1]
We further demonstrated that hexokinase-2 partly accounted for interleukin-22mediated cellular proliferation in DLD-1 cells
Our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells
Summary
Colorectal cancer (CRC) ranks as the third most common cancer and the fourth leading cause of death in the world [1]. The lack of an effective therapy leads to tumor recurrence and metastasis after surgery. There is an urgent need to understand molecular mechanisms underlying the development and progression of CRC. In contrast to normal cells, cancer cells rely on glycolysis as the main source of energy, regardless of oxygen availability, a phenomenon referred to as aerobic glycolysis (the Warburg effect) [2]. The Warburg effect has been well known for some time, the underlying mechanisms have remained largely elusive. Deciphering the underlying mechanism by which cancer cells adopt aerobic glycolysis could potentially contribute to understanding the biological characteristic of tumor cells and aid in the development of therapies to treat human malignancies [10]
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