Abstract 5201: Suppression of WNT1 expression inhibits the maintenance and expansion of cancer stem cells in a mouse model of breast cancer

Abstract

Abstract Cancer relapse is the most common cause of mortality in breast cancer patients. The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer. CSC-targeted therapies may prevent cancer relapse and provide more effective treatment. It has been known that stem cells can be enriched in non-adherent sphere culture. To identify molecular targets in breast CSC, we compared transcription levels of stem cell-related genes between tumorspheres established from Balb/c mice-derived 4T1 mammary carcinoma and mammospheres from the mammary glands of Balb/c mice. The most differentially expressed gene was found to be Wingless-type MMTV integration site family, member 1 (WNT1). To determine whether WNT1 has any relevance in breast carcinoma, we analyzed the expression of WNT1 in the human matched normal breast and breast cancer samples. Immunofluorescent staining showed that WNT1 expression was elevated ∼17-63-fold in cancerous tissues compared with non-cancerous tissues from the same breast cancer patients. Functionally, knockdown of WNT1 in 4T1 cells reduced the Aldefluorpos cell compartment enriched in CSCs and suppressed the properties of CSCs, including anti-apoptosis, sphere-forming ability, and tumor initiation ability in vivo. Collectively, these results show that WNT1 expression gives rise to properties of CSC in breast cancer. Therefore, the targeting of WNT1-associated signaling may provide an effective therapeutic approach in the treatment of advanced breast cancer. 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 5201. doi:1538-7445.AM2012-5201