title: The Enrichment of Survivin in Exosomes from Breast Cancer Cells Treated with Paclitaxel Promotes Cell Survival and Chemoresistance.
abstract: The generation and release of membrane-enclosed packets from cancer cells, called extracellular vesicles (EVs), play important roles in propagating transformed phenotypes, including promoting cell survival. EVs mediate their effects by transferring their contents, which include specific proteins and nucleic acids, to target cells. However, how the cargo and function of EVs change in response to different stimuli remains unclear. Here, we discovered that treating highly aggressive MDAMB231 breast cancer cells with paclitaxel (PTX), a chemotherapy that stabilizes microtubules, causes them to generate a specific class of EV, namely exosomes, that are highly enriched with the cell survival protein and cancer marker, Survivin. Treating MDAMB231 cells with a variety of other chemotherapeutic agents, and inhibitors that block cell growth and survival, did not have the same effect as PTX, with the exception of nocodazole, another inhibitor of microtubule dynamics. Exosomes isolated from PTX-treated MDAMB231 cells strongly promoted the survival of serum-starved and PTX-treated fibroblasts and SKBR3 breast cancer cells, an effect that was ablated when Survivin was knocked-down from these vesicles using siRNA. These findings underscore how the enrichment of a specific cargo in exosomes promotes cell survival, as well as can potentially serve as a marker of PTX resistance.
authors.affiliation: Department of Molecular Medicine, Cornell University, Ithaca, NY 14850, USA. btk37@cornell.edu.
authors.forename: Bridget T
authors.initials: BT
authors.lastname: Kreger
authors.affiliation: Department of Molecular Medicine, Cornell University, Ithaca, NY 14850, USA. ej95@cornell.edu.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Johansen
authors.affiliation: Department of Molecular Medicine, Cornell University, Ithaca, NY 14850, USA. rac1@cornell.edu.|Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14850, USA. rac1@cornell.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cerione
authors.affiliation: Department of Molecular Medicine, Cornell University, Ithaca, NY 14850, USA. maa27@cornell.edu.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Antonyak
keywords: Survivin; cell signaling; chemoresistance; chemotherapy; exosomes; extracellular vesicles; intercellular communication; paclitaxel; tumor microenvironment