ELF3-CaM interaction promotes angiogenic activity of ovarian cancer under hypoxic conditions


Session type:


Seung Hee Seo1



Ovarian cancer (OC) is one of the most common fatal gynecological cancer. Angiogenesis promotes metastasis, thereby reducing patient survival rates. Recently, ELF3 has been reported to be involved in the progression of various carcinomas. In public database analysis, OC patients with high ELF3 expression are associated with low survival rates.


To evaluate the association between ELF3 and HIF-1α, we applied ChIP and luciferase assay. To identify the impact of ELF3 in angiogenesis, angiogenic activity was assessed in HUVECs using conditioned media collected from ELF3-overexpressed and -silenced OC cells. Matrigel plug assay was performed in mice for further validation. To find co-activator for ELF3 to promote angiogenesis, we performed yeast two hybrid analysis, biosensor and IP assays, and western blot analysis in SKOV3 cells.


HIF-1α has been known to regulate various transcription factors to promote angiogenesis. We newly discovered that HIF-1α directly enhanced ELF3 promotor activity in OC cells. ELF3 increased mRNA and protein level of pro-angiogenic factors. When conditioned media of ELF3-overexpressed OC cells were applied to HUVEC, migration was accelerated along with increased angiogenic markers. ELF3-silencing prevented blood vessel formation in mice which was indicated by decrease in both hemoglobin concentration and CD31 level. We discovered calmodulin (CaM) as a novel co-activator for ELF3 to promote angiogenesis. We proved that CaM binds to the TAD domain of ELF3. The ELF3-CaM interaction was increased along with CaM activity and consequently, the function of ELF3 as a transcription factor was enhanced to promote pro-angiogenic factors.


ELF3, transcriptionally enhanced by HIF-1α in hypoxic condition, increased expression of pro-angiogenic factors in OC cells. In this process, CaM promoted the ELF3 function, thereby accelerating angiogenesis. Thus, Inhibiting the ELF3-CaM interaction may be an attractive therapeutic target for OC metastasis.