Purpose: Caveolin-1(CAV1), a membrane constituent protein, exhibits tumor suppressor activities in multiple malignancies, whereas the underlying mechanisms remain unclear. The current study aimed to determine the significance of CAV-1 in regulating cancer metabolism and its relation to breast cancer stem cells (CSCs).

Experimental Design: The anti-carcinogenic function of CAV1 was evaluated by in vitro cell model, CAV1 knockout mice and MMTV-PyMT spontaneous breast cancer xenografts. Glycolysis activity and mitochondrial metabolism were assessed by immunoblotting, oxygen consumption and mitotacker staining analysis. Mammosphere formation, tumorigenic ability, reattachment differentiation and signaling pathway analysis were applied to study the regulation effects of CAV1 on breast CSCs. The clinical significance of CAV1 was also analyzed by human tissue microarray.

Results: In both mammary transformed cells and spontaneous breast cancer xenografts, CAV1 is found significantly downregulated and positively correlated to increased glycolysis activity and impaired mitochondrial metabolism. Cav1 knockout results in increased ductal hyperplasia, associating with increased stem cell population and glycolysis metabolism. Breast CSCs exhibits glycolytic phenotype and decreased CAV1 expression compared to normal mammary stem cells, and CAV1 overexpression significantly limits CSCs’ self-renewal via inhibiting c-myc induced glycolysis. Clinical investigation suggests that high CAV1 expression is revealed with better overall survival and decreased CSCs population.

Conclusions: CAV1 loss facilitates mammary carcinogenesis via enhancing glycolytic activity in breast CSCs, and CAV1 based therapy might become a novel strategy for breast cancer prevention.

Note: This abstract was not presented at the meeting.

Citation Format: Zhiyu Wang, Neng Wang, Shengqi Wang, Yifeng Zheng. Caveolin-1 inhibits mammary carcinogenesis via suppressing c-myc-induced metabolism reprogramming in breast cancer stem cells [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 1924. doi:10.1158/1538-7445.AM2017-1924