Abstract 3317: The roles of TMCC3 in breast cancer cells

Abstract

Abstract There is growing evidence showing that cancer stem cells are more likely to metastasize and are more frequently detected in the circulation. Thus, it will be important to understand the molecular characteristics of breast cancer stem cells (BCSCs) which may lead to the development of novel targets for CSC-directed therapy. Through phosphoproteomic analysis of BCSC and non-BCSC, we identified differential expression of the transmembrane and coiled-coil domain family 3 (TMCC3). TMCC3 belongs to TEX28 family and is predicted to be an integral membrane protein. The function of TMCC3 is unknown. We found higher expression of TMCC3 in invasive breast cancer cell line and BCSCs than less-invasive breast cancer cell lines, and non-BCSCs, respectively. In addition, TMCC3 expression was greater in distant lymph node metastasis than in primary tumor of human breast cancer xenograft in mouse. Silencing of TMCC3 led to G1 phase arrest with increased apoptotic cells, along with decreased mammosphere formation and ALDH activity which are important features of cancer stem cell. In our previous investigation, the IGF-1R/PI3K/Akt/mTOR pathway was shown to be important for BCSCs survival and maintenance. To explore the possible involvement of TMCC3 in this pathway, we further examined the Akt and mTOR activation in TMCC3-slienced BCSCs. We found the Akt phosphorylation was lost in BCSCs upon TMCC3 knocked down. These findings suggest that TMCC3 is essential for breast cancer cell survival, self-renewal and metastasis. Thus, inhibition of TMCC3 may provide a new therapeutic strategy targeting stem cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3317. doi:1538-7445.AM2012-3317