Abstract 1278: Popdc proteins: novel targets in inhibiting breast cancer cell migration and proliferation

Abstract

Abstract Tumour growth and metastasis are major challenges in cancer treatment and metastasis is the primary cause of death in more than 90% of cancer patients with solid tumours (Gupta & Massagué 2006). This necessitates identification and validation of clinically relevant anticancer therapeutic targets that result in maximum clinical efficacy with minimal side-effects when manipulated by drugs. Our research project has identified Popeye domain containing (Popdc) proteins as promising potential therapeutic targets in the treatment of breast cancer. Popdc proteins are a class of membrane-tethered proteins encoded by the three members of the Popdc gene family Popdc1, Popdc2 and Popdc3. Their suppression has been correlated with disease progression and poor clinical outcomes in various cancers including breast cancer, gastric cancer, lung cancer, hepatocellular carcinoma and colorectal cancer (Kim et al., 2010, Luo et al., 2012, Williams et al., 2011, Wang et al., 2011). Loss of Popdc protein expression has been correlated with increased cancer cell migration, invasion, metastasis, drug-resistance and poor patient survival (Luo et al., 2012, Williams et al., 2011, Han et al., 2014). In breast cancer, Popdc1 suppression has been reported in breast carcinoma cells while upregulation of Popdc2 has been linked to the mechanism by which arsenic trioxide mediates breast cancer cell death (Williams et al., 2011, Wang et al., 2011). Our use of various assays including single-cell migration assays, cell population migration assays, cell proliferation assays and fluorescent imaging strongly implicate Popdc proteins as drivers of cancer cell migration and proliferation. Expression patterns of Popdc proteins revealed high expression levels in non-malignant (HMepC) breast cells and low expression in breast cancer (MCF7) cells. This suggests that loss of Popdc protein expression correlates with an increasingly malignant phenotype. Furthermore, knocking down Popdc1, Popdc2 and Popdc3 in MCF7 breast cancer cells significantly promoted cell migration both at single cell and at cell population level while Popdc2 knockdown significantly promoted unstimulated MCF7 cell division. Taken together, this strong data set suggests that Popdc proteins play significant roles in the migration and proliferation of different cancer cell lines and that they indeed represent promising potential therapeutic targets in reducing breast cancer cell division and migration. Citation Format: Johanna N. Amunjela, Steven J. Tucker. Popdc proteins: novel targets in inhibiting breast cancer cell migration and proliferation. [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 1278.