Abstract 4767: Identifying CDCA7 as a novel regulator of tumor-initiating cells in triple-negative breast cancer

Tumor-initiating cells (TICs) are a small fraction of cancer cells that stands at the apex of the tumor hierarchy. Given their tumor-initiating ability and resistance to conventional chemotherapies, TICs are considered potential therapeutic targets for preventing the relapse and metastasis of malignancies. Our group has identified a novel gene, Cell division cycle associated 7 (CDCA7), as an important regulator of TICs in triple-negative breast cancer (TNBC). CDCA7 is a target gene of MYC and NOTCH. Ectopic expression of CDCA7 has been demonstrated to induce neoplastic transformation in vitro and tumorigenesis in vivo. Despite its potential tumor-initiating ability, CDCA7 has not yet been well-studied in breast cancer. We found that CDCA7 was highly expressed in TNBC compared to other subtypes of breast cancer according to the RNA-sequencing data from The Cancer Genome Atlas. Furthermore, our Kaplan-Meier analysis of multiple datasets demonstrated that higher expression of CDCA7 was associated with poor prognosis in breast cancer. When we knocked down CDCA7 by siRNA in TNBC cell lines including SUM149, HCC1937, MDA-MB-231, and MDA-MB-436, CD44+/CD24- stem-like cell population and primary and secondary mammosphere formation were significantly decreased. In addition to suppressing the stem-like properties, knockdown of CDCA7 also inhibited the invasion and migration of breast cancer cells. These phenotypes indicated the inhibition of epithelial-to-mesenchymal transition (EMT), which was in accordance with the up-regulation of E-Cadherin and down-regulation of Vimentin after CDCA7 knockdown in TNBC cell lines. In conclusion, our results have demonstrated that CDCA7 is an important regulator of TICs in TNBC. Loss-of-function of CDCA7 leads to the inhibition of EMT and stemness in TNBC cells. Citation Format: Chang-Ching Lin, Miao-Chia Lo, Rebecca Moody, Nicholas Stevers, Samantha Tinsley, Max Wicha, Duxin Sun. Identifying CDCA7 as a novel regulator of tumor-initiating cells in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4767. doi:10.1158/1538-7445.AM2017-4767