The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma.

The interaction of LOXL2 with GATA6 induces VEGFA expression and angiogenesis in cholangiocarcinoma. Int J Oncol. 2019 Jul 15;: Authors: Peng T, Deng X, Tian F, Li Z, Jiang P, Zhao X, Chen G, Chen Y, Zheng P, Li D, Wang S Abstract Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer after hepatocellular carcinoma. Antiangiogenic therapy has been administered to patients with CCA, but the benefits of this therapy remain unsatisfactory. Improved understanding of the molecular mechanisms underlying angiogenesis in CCA is required. In the present study, the expression of GATA‑binding protein 6 (GATA6), lysyl oxidase‑like 2 (LOXL2) and vascular endothelial growth factor A (VEGFA), in addition to the microvessel density (MVD), were evaluated by performing immunohistochemical staining of human CCA microarrays. The expression of GATA6/LOXL2 was associated with poor overall survival (P=0.01) and disease‑free survival (P=0.02), and was positively associated with VEGFA expression (P=0.02) and MVD (P=0.04). In vitro, western blotting, reverse transcription‑quantitative PCR analysis and ELISAs revealed that altered GATA6 and LOXL2 expression regulated the expression levels of secreted VEGFA. Co‑immunoprecipitation demonstrated a physical interaction between GATA6 and LOXL2 in CCA cell lines, and the scavenger receptor cysteine‑rich domain of LOXL2 interacted with GATA6, which regulated VEGFA mRNA expression ...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research