Role of enolase-1 in response to hypoxia in breast cancer: Exploring the mechanisms of action

Abstract

In the present study, we investigated the effect of reduced enolase-1 expression in human umbilical vein endothelial cells (HUVECs)/MDA-MB-231 cells on the response to hypoxia and the possible mechanisms involved. Breast cancer cells transfected with enolase-1 siRNA were injected into mice to establish a tumor-bearing mouse model, and the correlation between enolase-1 expression and breast cancer angiogenesis, as well as its effect on the efficacy of radiation therapy were assessed. HUVECs were cultured in vitro, and transfected with enolase-1 siRNA. Following stable passage, 1.0% O2 was used to induce hypoxia. The growth, proliferation, division and angiogenesis of HUVECs were observed using MTT assay, flow cytometry (FCM) and time-lapse video microscopy. The key regulatory molecules were detected using western blot analysis, two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The breast cancer cell line, MDA-MB-231, was cultured in vitro, and transfected with enolase-1 siRNA. The cells were injected into nude mice, and radiation therapy was administered. Tumor growth, angiogenesis in tumor tissues and apoptosis were observed, and the expression of the endogenous hypoxia marker, hypoxia inducible factor-1α (HIF-1α), was detected using immunohistochemistry after the mice were sacrificed. A significant reduction in the hypoxia-induced apoptosis of HUVECs was observed in the control group compared with the endothelial cells transfected with enolase-1 siRNA. After the enolase-1 transfected breast cancer cells were injected into nude mice, tumor growth significantly declined, and the tumor volume and weight were reduced. Following treatment with radiation therapy, tumor size significantly decreased in both groups, and the highest reduction was observed in the transfected group. The reduction in enolase-1 expression significantly decreases the response to hypoxia and enhances the sensitivity of the cells to radiation therapy; therefore, enolase-1 may be a drug target for the treatment of breast cancer.

Enolase1 overexpression regulates the growth of gastric cancer cells and predicts poor survival

“…In many tumors, ENO1 promoted the proliferation of cancer cells . Indeed, we observed that ENO1 knockdown reduced the rate of proliferation and capacity of colony formation in MKN‐45 cells and MGC‐803.…”

“…Within cells, ENO1 is predominantly localized to the cytoplasm. In addition, this protein also has an alternatively translated form that is localized to the nucleus . As a glycolytic enzyme, ENO1 catalyzes the conversion of phosphoenolpyruvate generation from 2‐phosphoglycerate .…”

Defining the Na+/H+ exchanger NHE1 interactome in triple-negative breast cancer cells

“…α-enolase is a cytosolic glycolytic enzyme and oxidative stress protein. Its expression is elevated in many tumours, including those of the breast, where it is also found on the cell surface [46,47]. The NHE1-α-enolase complex was confirmed by both affinity chromatography and co-immunoprecipitation.…”

FBXW7 negatively regulates ENO1 expression and function in colorectal cancer

“…Many reports have demonstrated that ENO1 can be regulated at different levels by multiple factors. For example, ENO1 can be transcriptionally activated by NFκB, 8 HIF-1α 4 and estrogen receptor (ER) α, 2,8 while it also can be downregulated by retinoic acid at the protein level. 39 Moreover, Yu et al 2 observed that estradiol prolongs ENO1 protein half-life and increases ENO1 protein accumulation via a posttranscriptional mechanism.…”