LOXL2 upregulates hypoxia ‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells.

LOXL2 upregulates hypoxia‑inducible factor‑1α signaling through Snail‑FBP1 axis in hepatocellular carcinoma cells. Oncol Rep. 2020 Mar 10;: Authors: Fan Z, Zheng W, Li H, Wu W, Liu X, Sun Z, Hu H, Du L, Jia Q, Liu Q Abstract Lysyl oxidase‑like 2 (LOXL2), a member of the lysyl oxidase gene family, is involved in the progression of hepatocellular carcinoma progression and metastasis. Increased expression of LOXL2 has been identified in several types of cancer, including hepatocellular carcinoma. Recently, LOXL2 has been reported to promote epithelial‑mesenchymal transition by reducing E‑cadherin expression via the upregulation of Snail expression. The present study provided evidence demonstrating that LOXL2 inhibited the expression of fructose‑1, 6‑biphosphatase (FBP1) and enhanced the glycolysis of Huh7 and Hep3B hepatocellular carcinoma cell lines in a Snail‑dependent manner. Overexpression of the point‑mutated form of LOXL2 [LOXL2(Y689F)], which lacks enzymatic activity, does not affect the expression of Snail1 or FBP1. Notably, targeting extracellular LOXL2 of Huh7 cells with a therapeutic antibody was unable to abolish its regulation on the expression of Snail and FBP1. Knockdown of LOXL2 also interrupted the angiogenesis of Huh7 and Hep3B cells, and this effect could be rescued by the overexpression of Snail. Furthermore, upregulation of hypoxia‑inducible factor 1α (HIF‑1α) and vascular endothelial gr...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research