Panoply™ Human LIF Over-expressing Stable Cell Line

LIF is a multifunctional cytokine frequently overexpressed in various solid tumors, including breast cancer, and plays a crucial role in promoting tumorigenesis. The mechanisms by which LIF drives tumorigenesis remain incompletely understood. Metabolic reprogramming is a hallmark of cancer cells and a key driver of cancer progression; however, the role of LIF in cancer metabolic reprogramming is unclear. Here, researchers found that LIF promotes breast tumorigenesis by increasing glucose uptake and driving glycolysis. Blocking glucose uptake significantly abolishes the promoting effect of LIF on breast tumorigenesis. Mechanistic studies revealed that LIF overexpression enhances glucose uptake-and subsequently glycolysis-by activating the AKT/GLUT1 axis. Blocking the AKT signaling pathway using shRNA or inhibitors significantly suppresses LIF-driven glycolysis and largely eliminates the promoting effect of LIF on breast tumorigenesis. These results demonstrate that LIF overexpression plays a vital role in glucose metabolic reprogramming in breast cancer and drives breast tumorigenesis. This study uncovers a key mechanism underlying metabolic reprogramming in breast cancer and identifies LIF and its downstream signaling pathways as potential therapeutic targets for breast cancer, particularly in cases characterized by high LIF expression.

Previous studies have shown that elevated glucose uptake and glycolysis are key factors driving cancer cell proliferation and tumor progression. Here, the researchers investigated whether the ability of LIF (leukemia inhibitory factor) to promote glucose uptake and glycolysis underlies its pro-tumorigenic function. LIF overexpression promoted the proliferation of MCF7, MDA-MB 231, and T47D cells (Figure 1A). The glucose analogue 2-DG inhibits glucose transport and glycolysis by competing with glucose. Experiments demonstrated that 2-DG treatment inhibited the proliferation of MCF7, MDA-MB 231, and T47D cells in a dose-dependent manner (Figure 1A). Notably, LIF-overexpressing breast cancer cells were more sensitive to 2-DG treatment than control cells (Figure 1B). The researchers further compared the effects of 2-DG treatment on the growth of subcutaneous xenograft tumors derived from MCF7 and MDA-MB 231 cells (with or without ectopic LIF expression). The results showed that LIF overexpression promoted the growth of xenograft tumors derived from MCF7 and MDA-MB 231 cells (Figure 1B). Although 2-DG treatment inhibited xenograft tumor growth, this inhibitory effect was more pronounced in LIF-overexpressing tumors (Figure 1B). Collectively, these results indicate that LIF promotes cell proliferation and tumor growth by enhancing glucose uptake and glycolysis in breast cancer cells.

Figure 1. 2-DG, a glycolysis inhibitor, preferentially inhibits the proliferation of breast cancer cells and the growth of xenograft tumors with LIF overexpression. (Yue X, et al., 2022)