Page 156 - D. Cancer biology

[D. Cancer biology-100]

GPR110 plays a critical role in regulation of triple-negative

breast cancer progression

Hye-Jung Nam¹, Eun-Ji Lim¹, Yi Zhao¹, Su-Jae Lee¹

¹Department of Life Science, Hanyang University, Seoul 04763, Republic of Korea

Triple negative breast cancer (TNBC) which is a group of breast cancer correlates with aggressive behaviors and
poor clinical outcomes. TNBC remains intractable to targeted therapies because lacking of estrogen receptor (ER),
progesterone receptor (PR) and human epidermal growth factor receptor2 (HER2) expression. Thus, development

of targeted therapies becomes a significant issue in the treatment of TNBC. Here, we report that GPR110 among

adhesion GPCR (aGPCR) is required for maintenance of TNBC type features. Importantly, TCGA and GSEA database
showed that GRP110 expression in TNBC is higher than luminal type of breast cancer and high expression of GRP110
correlates with poor outcomes. Loss of GPR110 expression could inhibit invasiveness and stemness of TNBC.

Moreover, through the screening of a variety of small GTPases, we find that K-Ras acts as a downstream mediator
of GPR110, and consequently regulates EMT and stemness in TNBC. Taken together, our findings demonstrate a

crucial role of GPR110 and its downstream effectors in maintaining the TNBC type features in breast cancer, and
we suggest that GPR110 would be a putative therapeutic target for TNBC treatment.