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. 2018 Sep 5;131(17):jcs217760. doi: 10.1242/jcs.217760

Fig. 8.

Fig. 8.

A model for cancer cell adaptation to Hsp70 inhibition. MAL3-101 treatment of RMS13 cells inhibits Hsp70 activity and induces (1) the accumulation of unfolded proteins that (2) lead to PERK-mediated transcription of ATF4 and CHOP, which (6) results in cell death (Sabnis et al., 2016). In contrast, (3) higher steady state levels of autophagy and perhaps an ATF4-mediated increase in ATG gene expression upon MAL3-101 treatment in RMS13-R cells (4) protects against cell death and favors cancer cell survival. If, however, autophagy is impaired [for example by CQ (5)], (6) Hsp70 inhibition is again toxic to MAL3-101-resistant cancer cells, which results in apoptosis.