Abstract 2080: Plasma membrane fluidity drives metastasis in breast cancer

Published on Oct 1, 2014in Cancer Research9.727
· DOI :10.1158/1538-7445.AM2014-2080
Weina Zhao3
Estimated H-index: 3
(University of Texas Health Science Center at Houston),
Michael J. Tisza7
Estimated H-index: 7
(University of Texas Health Science Center at Houston)
+ 2 AuthorsJeffrey T. Chang41
Estimated H-index: 41
(University of Texas Health Science Center at Houston)
Sources
Abstract
Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA New therapeutic targets that can inhibit cancer metastasis are desperately needed. To address this issue, we have leveraged a computational approach and performed an unbiased screen for therapies that can inhibit an epithelial-to-mesenchymal transition (EMT) gene expression profile, a phenotype that is believed to promote metastases. This yielded predictions of drugs that can both promote and inhibit an EMT transcriptional profile. Following up on these predictions, we confirmed that these drugs can induce or repress an EMT in a range of breast cancer cell lines. Furthermore, we discovered that they do so by altering the fluidity of the plasma membrane. An increase in plasma membrane fluidity is necessary and sufficient to induce and maintain an EMT state, increased motility, and increased mammosphere forming ability. Finally, we found that human cancers can regulate their membrane fluidity through cholesterol homeostasis pathways. Human breast tumors with altered cholesterol profiles have a significantly shorter time to metastasis. These data demonstrate that plasma membrane fluidity is a cellular attribute that is leveraged by human tumors to increase metastatic capacity, and that it can, in principle, be targeted by therapeutics to prevent metastasis. Citation Format: Weina Zhao, Michael Tisza, Jessie Sjol, Sendurai Mani, Jeffrey T. Chang. Plasma membrane fluidity drives metastasis in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2080. doi:10.1158/1538-7445.AM2014-2080
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