PT  - JOURNAL ARTICLE
AU  - Berdan, Charles A.
AU  - Ho, Raymond
AU  - Lehtola, Haley S.
AU  - To, Milton
AU  - Hu, Xirui
AU  - Huffman, Tucker R.
AU  - Petri, Yana
AU  - Altobelli, Chad R.
AU  - Demeulenaere, Sasha G.
AU  - Olzmann, James A.
AU  - Maimone, Thomas J.
AU  - Nomura, Daniel K.
TI  - Parthenolide Covalently Targets and Inhibits Focal Adhesion Kinase in Breast Cancer Cells
AID  - 10.1101/550806
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 550806
4099  - http://biorxiv.org/content/early/2019/02/14/550806.1.short
4100  - http://biorxiv.org/content/early/2019/02/14/550806.1.full
AB  - 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. Herein, we further study parthenolide mechanism of action using activity-based protein profiling (ABPP)-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 (C427) 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 novel functional target exploited by members of a large family of anticancer natural products.