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. 2019 Aug 30;11(9):1272. doi: 10.3390/cancers11091272

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Schematic representation of the mechanism for cancer induction of muscle wasting through the release of EV-associated Hsp70 and Hsp90 that activate TLR4 on muscle cells. (1) Multivesicular bodies (MVBs) in tumor cells fuse with the plasma membrane releasing EVs (orange balls). (2) Circulating EVs carry surface Hsp70 and Hsp90 (purple loops). (3) Hsp70/90-carrying EVs activate TLR4 on muscle cells. (4) TLR4 activation of p38β MAPK upregulates rate-limiting genes in UPP and ALP via C/EBPβ.