Fig. 1 Multivalent proapoptotic DRAs can induce cell death in TRAIL-sensitive and TRAIL-resistant human CRC cell lines. Multivalent proapoptotic DRAs can.

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Fig. 1 Multivalent proapoptotic DRAs can induce cell death in TRAIL-sensitive and TRAIL-resistant human CRC cell lines. Multivalent proapoptotic DRAs can induce cell death in TRAIL-sensitive and TRAIL-resistant human CRC cell lines. (A) The DRA is composed of oligomers of the third type III fibronectin domain of tenascin engineered to bind DR5 with a KD (dissociation constant) = 43 nM for the DRA monomer, linked by flexible glycine-serine linkers (G4S)3 and expressed recombinantly in E. coli (10). Monomers and dimers do not induce cell death (top), whereas the hexameric DRA increases apoptotic signaling in sensitive cell lines (bottom). (B and C) Human CRC cell lines’ responses to DRA treatment are superior to TRAIL in TRAIL-sensitive cell lines HCT116 and Colo205. (D) DRAs can induce cell death in TRAIL-resistant cell line HT29 cells. (E) RKO cells are resistant to both TRAIL and DRA treatment. Mandana T. Manzari et al. Sci Adv 2019;5:eaaw9162 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).