Panoply™ Human LOXL2 Knockdown Stable Cell Line

Lysyl oxidase‑like 2 (LOXL2) is a member of the lysyl oxidase gene family and is involved in the progression and metastasis of hepatocellular carcinoma (HCC). LOXL2 is highly expressed in various cancers, including HCC. Recent studies have shown that LOXL2 can promote epithelial-mesenchymal transition (EMT) by upregulating Snail expression and reducing E-cadherin expression. Here, researchers demonstrate that LOXL2 inhibits fructose-1,6-bisphosphatase (FBP1) expression in a Snail-dependent manner and enhances glycolysis in Huh7 and Hep3B HCC cancer cell lines. Overexpression of the LOXL2 point mutant [LOXL2(Y689F)] lacking enzyme activity does not affect Snail1 or FBP1 expression. Notably, targeting extracellular LOXL2 in Huh7 cells with therapeutic antibodies does not eliminate its regulatory effect on Snail and FBP1 expression. Knockdown of LOXL2 also inhibited angiogenesis in Huh7 and Hep3B cells, while overexpression of Snail reversed this effect. Furthermore, upregulation of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) was observed in Huh7 and Hep3B cells expressing wild-type LOXL2. Notably, the selective LOXL2 inhibitor LOXL2-IN-1 upregulated FBP1 expression in HCC cells and inhibited the expression of Snail, HIF-1α, and VEGF, but this effect was not observed in FBP1 knockdown cells. These results indicate that the intracellular activity of LOXL2 upregulates the HIF-1α/VEGF signaling pathway via the Snail-FBP1 axis, and inhibition of LOXL2 suppresses this phenomenon.

Here, researchers investigated whether knocking down LOXL2 affected the expression level of FBP1 in hepatocellular carcinoma cells. As shown in Figure 1A, knocking down LOXL2 significantly inhibited Snail expression. Furthermore, FBP1 expression was upregulated in LOXL2-knockdown Huh7 and Hep3B hepatocellular carcinoma cells (Figure 1A). Further investigation revealed that overexpression of wild-type LOXL2 increased Snail expression and inhibited FBP1 expression (Figure 1B). Notably, overexpression of the enzyme-deficient point mutant LOXL2 [LOXL2(Y689F)] did not affect Snail1 or FBP1 expression (Figure 1B).

Figure 1. Intracellular LOXL2 inhibits the expression of FBP1. (Fan Z, et al., 2020)