Anti-GABPA polyclonal antibody

Background: Increasing evidence indicates that abnormal expression of GABPA is associated with tumor development and progression. However, the function and clinicopathological significance of GABPA in hepatocellular carcinoma (HCC) remain obscure. Methods: The mRNA and protein expression of GABPA in HCC clinical specimens and cell lines was examined by real-time PCR and western blotting, respectively. Follow-up data were used to uncover the relationship between GABPA expression and the prognosis of HCC patients. HCC cell lines stably overexpressing or silencing GABPA were established to explore the function of GABPA in HCC cell migration and invasion by Transwell and wound healing assays in vitro and in a xenograft model in vivo. Restoration of function analysis was used to examine the underlying molecular mechanisms. Results: GABPA was downregulated at the protein and mRNA levels in HCC tissues compared with adjacent normal tissues. Decreased GABPA expression was correlated with alpha-fetoprotein levels (P = 0.001), tumor grade (P = 0.017), and distant metastasis (P = 0.021). Kaplan-Meier survival analysis showed that patients with lower GABPA expression had significantly shorter survival times than those with higher GABPA (P = 0.031). In vivo and in vitro assays demonstrated that GABPA negatively regulated HCC cell migration and invasion, and the effect of GABPA on HCC cell migration was mediated at least partly by the regulation of E-cadherin. Conclusions: Collectively, our data indicate that GABPA inhibits HCC cell migration by modulating E-cadherin and could serve as a novel biomarker for HCC prognosis. GABPA may act as a tumor suppressor during HCC progression and metastasis, and is a potential therapeutic target in HCC.

TERT promoter mutations occur in the majority of glioblastoma, bladder cancer (BC), and other malignancies while the ETS family transcription factors GABPA and its partner GABPB1 activate the mutant TERT promoter and telomerase in these tumors. GABPA depletion or the disruption of the GABPA/GABPB1 complex by knocking down GABPB1 was shown to inhibit telomerase, thereby eliminating the tumorigenic potential of glioblastoma cells. GABPA/B1 is thus suggested as a cancer therapeutic target. However, it is unclear about its role in BC. Here we unexpectedly observed that GABPA ablation inhibited TERT expression, but robustly increased proliferation, stem, and invasive phenotypes and cisplatin resistance in BC cells, while its overexpression exhibited opposite effects, and inhibited in vivo metastasizing in a xenograft transplant model. Mechanistically, GABPA directly activates the transcription of FoxA1 and GATA3, key transcription factors driving luminal differentiation of urothelial cells. Consistently, TCGA/GEO dataset analyses show that GABPA expression is correlated positively with luminal while negatively with basal signatures. Luminal tumors express higher GABPA than do basal ones. Lower GABPA expression is associated with the GABPA gene methylation or deletion (especially in basal subtype of BC tumors), and predicted significantly shorter patient survival based on TCGA and our cohort of BC patient analyses. Taken together, GABPA dictates luminal identity of BC cells and inhibits aggressive diseases in BC by promoting cellular differentiation despite its stimulatory effect on telomerase/TERT activation. Given these biological functions and its frequent methylation and/or deletion, GABPA serves as a tumor suppressor rather than oncogenic factor in BC. The GABPA effect on oncogenesis is context-dependent and its targeting for telomerase inhibition in BC may promote disease metastasizing.