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Article Publish Status: FREE
Abstract Title:

Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells.

Abstract Source:

Cell Chem Biol. 2019 Jul 18 ;26(7):1027-1035.e22. Epub 2019 May 9. PMID: 31080076

Abstract Author(s):

Charles A Berdan, Raymond Ho, Haley S Lehtola, Milton To, Xirui Hu, Tucker R Huffman, Yana Petri, Chad R Altobelli, Sasha G Demeulenaere, James A Olzmann, Thomas J Maimone, Daniel K Nomura

Article Affiliation:

Charles A Berdan

Abstract:

Parthenolide, a natural product from the feverfew plant and member of the large family of sesquiterpene lactones, exerts multiple biological and therapeutic activities including anti-inflammatory and anti-cancer effects. Here, we further study the parthenolide mechanism of action using activity-based protein profiling-based chemoproteomic platforms to map additional covalent targets engaged by parthenolide in human breast cancer cells. We find that parthenolide, as well as other related exocyclic methylene lactone-containing sesquiterpenes, covalently modify cysteine 427 of focal adhesion kinase 1 (FAK1), leading to impairment of FAK1-dependent signaling pathways and breast cancer cell proliferation, survival, and motility. These studies reveal a functional target exploited by members of a large family of anti-cancer natural products.

Study Type : In Vitro Study

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