Abstract 1637: 22(S)-Hydroxycholesterol, an antagonist of LXR, inhibits breast cancer cell migration

Abstract The Liver X Receptor (LXR) is a well-established ligand-regulated transcription factor involved in cholesterol homeostasis, lipid metabolism, and inflammation. Recent studies have reported a strong antiproliferative effect of LXRs in multiple types of cancer including prostate, colon, lung, and breast cancer. However, little is known about its association with cancer metastasis. Therefore we aimed to investigate the potential of LXR ligands in the context of breast cancer cell migration, and its underlying molecular mechanism. We first performed 2D-migration assay in 4T1 breast cancer cells. Treatment of an LXR antagonist significantly reduced the rate of 4T1 cell migration. However, LXR agonists such as T0901317, GW3965 did not have much effect. Next, we investigated the molecular mechanism of cell migration. Since the degree of invasion and metastasis of breast carcinoma is well correlated with elevated expression of metastasis-associated protein 1 (MTA1), we examined whether MTA1 expression could be regulated by LXR ligands. Interestingly, when LXR agonists were treated, increased protein expression of MTA1 and its downstream target protein HIF-1α was observed in MCF7, MDA-MB-231, and 4T1-Luc breast cancer cell lines. Transient expression of LXRα demonstrated the same results as well. Furthermore, the treat of 22(S)-HC down-regulated MTA1 and HIF-1α protein expressions. Together, our findings indicate that LXR influences migratory pattern of breast cancer cells, which may affect metastatic property of breast cancer cells via LXR-dependent regulation of MTA1 and HIF-1α expression. Citation Format: Sewon Hwang, Tae Young Na, Hyelin Na, Minho Lee, Mi-Ock Lee. 22(S)-Hydroxycholesterol, an antagonist of LXR, inhibits breast cancer cell migration. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1637.